FI119988B - Cyclic hexapeptides with antibiotic activity - Google Patents

Description

Cyclic hexapeptides with antibiotic activity. - Cyk-Liska hexapeptider med antibiotic.

The present invention relates to a novel polypeptide compound and a pharmaceutically acceptable salt thereof which are useful as pharmaceuticals.

The U.S. Pat. Well. 5,376,634 discloses a polypeptide compound and a pharmaceutically acceptable salt thereof having antimicrobial activity (in particular antifungal activity).

The present invention relates to a novel polypeptide compound and a pharmaceutically acceptable salt thereof.

More particularly, it is directed to a novel dust peptide compound and a pharmaceutically acceptable salt thereof having anti-microbial activities [in particular antifungal activities in which fungi may be Aspergillus, Cryptococcus, Candida, Mucor, Actinomyces, Histoplasma, Dermatophyte, Malassez, Malassez inhibitory activity on β-1,3-glucan synthase, and further expected to be useful in the prophylactic and / or therapeutic treatment of Pneumocystis carinii infection (e.g., Pneumocystis carinii pneumonia) in a human or animal, for the preparation thereof, including and the use of a compound of the invention in the manufacture of a medicament for the treatment of infectious diseases including Pneumocystis carinii infection. , (e.g., Pneumocystis carinii pneumonia), in a human or animal.

; “· The subject polypeptide used in the present invention · <. the tide compound is new and can be represented by the following general formula [I]: 2 HO OH HO O \ —- /

Η3α- ^ Υ ^ ΝΗ ZnH-rI

'—N \ = 0

HO V = ° HN OH

K / ™ 0 = <J m H2n 0 = / Ν-Λ

HO) -NH / V

0 UK ΊΚ ^ 0 ”

Il / = \ 0H 0 HO-S-O - {\ />

Il V / O f-

HO

wherein R 1 is (C 1 -C 6) alkanoyl substituted by pyrazolyl having (C 1 -C 6) alkyl and phenyl having (C 7 -C 20) alkoxy; (C 1 -C 6) alkoxy (C 7 -C 20) alkanoyl, wherein (C 7 -C 20) alkanoyl may be amino or protected amino; benzoyl substituted with cyclo (C 4 -C 6) alkyl having (C 1 -C 6) alkyl; indolylcarbonyl having (C7-C20) alkyl; . : ', naphthoyl having (C 1 -C 6) alkyl; ! , naphthoyl having (C7-C20) alkyl; benzoyl substituted with phenyl having (C 1 -C 6) alkoxy (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; ; ··· benzoyl substituted with phenyl having (C 1 -C 6) -:; alkoxy (C1-C6) alkoxy; benzoyl substituted with phenyl having phenyl having (C 1 -C 6) alkoxy- (C 1 -C 6) alkoxy; benzoyl substituted with phenyl having tetrahydropy-1; 1 ranyloxy (C 7 -C 20) alkoxy; : benzoyl substituted with phenyl having phenoxy (C 1-4); (C 1 -C 6) alkanoyl substituted with oxazolyl containing phenyl having (C 7 -C 20) alkoxy; 1; (C 7 -C 20) alkanoyl having hydroxy; (C 7 -C 20) alkanoyl having benzyl and hydroxy; 3-methyl-tridekenoyyli; 3 (C 1 -C 6) alkanoyl substituted with pyridyl or pyridazinyl, each of which may have from 1 to 3 substituents selected from the group consisting of (C 7 -C 20) alkoxy, (C 7 -C 20) alkoxy (C 1 -C 6) ) - alkyl, phenyl having (C7-C20) alkoxy, phenyl substituted with phenyl having (C1-C6) alkoxy, piperazinyl substituted with phenyl having (C7-C20) alkoxy, piperazinyl substituted phenyl having (C 1 -C 6) alkoxy- (C 7 -C 20) alkoxy and piperazinyl substituted with phenyl having (C 1 -C 6) alkoxy; (C 1 -C 6) alkanoyl substituted with benzothiophenyl, which may have 1-3 (C 7 -C 20) alkoxy; (C 1 -C 6) alkanoyl substituted with benzo [b] furanyl which may have 1 to 3 substituents selected from the group consisting of (C 7 -C 20) alkoxy and (C 1 -C 6) alkyl; (Cx-C8) alkanoyl substituted with benzooxazolyl which may have 1 to 3 substituents selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl substituted phenyl having (C 1 -C 8) alkyl and pyridyl having (C 7 -C 20) alkoxy; (Cx-C8) alkanoyl substituted by piperidyl or piperazinyl, each of which may have from 1 to 3 substituents selected from the group consisting of phenyl having (C7-C20) alkoxy and naphthoyl having (C7- C 20) alkoxy; phenyl (C3-C6) alkenoyl substituted with phenyl which may have 1 to 3 substituents selected from the group consisting of (C1-C6) -, -alkoxy, (Cx-C6) alkyl, (C7-C20) alkyl , (C 1 -C 8) alkoxy (C 1 -C 6) alkyl, '' 'halogen (C 1 -C 6) alkoxy, (C 2 -C 6) alkenyloxy, halogen (C 7 -C 20) alkoxy; and (Cx-C8) alkoxy (C7-C20) alkoxy; naphthyl (C3-C6) alkenoyl, which may have 1-3 (C7-C20) alkoxy; 2-propynoyl (2- or 3-) butynoyl, (2- or 3- or 4-) pentynoyl, (2- or 3- or 4- or 5-) hexynoyl, each of which may have 1-3 substituents selected from comprising naphthyl having I (C7-C20) alkoxy and phenyl substituted with phenyl having (C1-C5) alkyl; -; phenyl (C 2 -C 5) alkanoyl substituted with phenyl having from 1 to 3 substituents selected from the group consisting of (C 1 -C 8) alkoxy, (C 7 -C 20) alkoxy, (C 1 -C 8) alkyl, (C 7 -C 20) ) alkyl and phenyl having (C 1 -C 6) alkoxy (C 2 -C 8) alkyl wherein the phenyl (C 2 -C 6) alkanoyl may be hydroxy, oxo, protected amino or amino; (C2-C6) alkanoyl substituted with naphthyl having (C7-C20) 4 alkoxy; benzoyl substituted with pyrrolidinyl, imidazolidinyl, piperidyl or piperazinyl, each of which may have from 1 to 3 substituents selected from the group consisting of phenyl having (C 1 -C 6) alkoxy, phenyl having (C 7 -C 20) alkoxy , phenyl having (C 1 -C 6) alkyl, phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, phenyl having (C 7 -C 20) alkenyloxy, piperidyl substituted with phenyl wherein is (C 1 -C 6) alkoxy, piperidyl, cyclo (C 4 -C 6) alkyl having phenyl, phenyl having cyclo (C 4 -C 6) alkyl and phenyl substituted with a triazolyl having oxo and (C 1 -C 6) alkyl; -C 6) alkyl wherein the benzoyl may be halogen; benzoyl substituted with oxazolyl, iso-oxazolyl or oxadiazolyl, each of which may have from 1 to 3 substituents selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl having (C 7 -C 20) alkoxy, phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, phenyl substituted with phenyl having (C 1 -C 6) alkoxy; benzoyl substituted with pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl or tetrazolyl, each of which may have 1-3 substituents selected from C, phenyl having (C 1 -C 6) alkoxy; benzoyl substituted with thiazolyl, isothiazolyl,; thiadiazolyl or dihydrothiazinyl, each of which may have from 1 to 3 substituents selected from the group consisting of phenyl, 1 'having (C 1 -C 6) alkoxy, phenyl having (C 7 -C 20) alkoxy, cyclo (C 4 -C 6) alkyl, wherein (C 1 -C 8) alkyl is phenyl substituted with phenyl; '. alkyl having (C 1 -C 8) alkoxy, phenyl having cyclo (C 4 -C 6) alkyl, phenyl having piperidine and phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; 'Benzoyl substituted with phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; benzoyl substituted with phenyl having (C 1 -C 8) alkyl; benzoyl substituted with phenyl having (C7-C20) alkyl; I, and a pharmaceutically acceptable salt thereof.

Preferably, the invention relates to polypeptide compounds wherein the substituent R1 is benzoyl substituted with piperazinyl which may have 1-3 substituents selected from the group consisting of phenyl having (C1-C6) alkoxy, phenyl having (C7- C 20) -alkoxy, phenyl having (C 1 -C 6) alkyl, phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, phenyl having (C 7 -C 20) alkenyloxy, piperidyl substituted phenyl having (C 1 -C 6) alkoxy, cyclo (C 4 -C 6) alkyl having phenyl, phenyl having cyclo (C 4 -C 6) alkyl, and phenyl substituted with a triazolyl having oxo and (C 1 -C 6) alkyl wherein benzoyl may have halogen; benzoyl substituted with iso-oxazolyl which may have 1-3 substituents selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, phenyl substituted with phenyl having (C 1 -C 6) alkoxy; benzoyl substituted with phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; benzoyl substituted with phenyl having (C 1 -C 6) alkyl; benzoyl substituted with phenyl having (C7-C20) alkyl; phenyl (C 3 -C 6) alkenoyl substituted with phenyl which may have 1 to 3 substituents selected from the group consisting of (C 1 -C 6) alkoxy, (C 1 -C 6) alkyl, (O 2 -O 2) alkyl, (C) C 1 -C 6 alkoxy (C 1 -C 6) alkyl, halogen (C 1 -C 6) alkoxy, (C 2 -C 6) alkenyloxy, halogen (C 7 -C 20) alkoxy and (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; benzoyl substituted with thiadiazolyl which may have 1 to 3 substituents selected from the group consisting of phenyl wherein. :, is (C 1 -C 8) alkoxy, phenyl having (C 7 -C 20) alkoxy, cyclo (C 4 -C 6) -, alkyl having (C 1 -C 6) alkyl, phenyl substituted with phenyl having (C 1 -C 6) alkyl. -C 6) alkoxy, phenyl having cyclo (C 4 -C 6) alkyl, phenyl having piperidyl, and phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; or benzoyl substituted with oxadiazolyl which may have '1-3 substituents selected from the group consisting of phenyl having (C 1 -C 6) alkoxy, phenyl having (C 7 -C 20) alkoxy, phenyl having 1'. (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, (C 7 -C 20) alkyl, and phenyl • substituted with phenyl having (C 1 -C 6) alkoxy.

: More preferably, the invention relates to polypeptide compounds wherein the substituent R1 is benzoyl substituted by phenyl wherein (C1-C6) alkoxy (C7-C20) alkoxy; or benzoyl substituted with phenyl having (C 2 -C 6) alkyl.

More preferably, the invention relates to polypeptide compounds wherein the substituent R 1 is benzoyl substituted by piperazinyl, which may be phenyl having (C 1 -C 6) alkoxy; 6 benzoyl substituted with isoxazolyl which may be phenyl having (C 1 -C 6) alkoxy; benzoyl substituted with thiadiazolyl which may be phenyl having (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; or benzoyl substituted with oxadiazolyl, which may be phenyl having (C 1 -C 6) alkoxy.

More preferably, the invention relates to polypeptide compounds,. Wherein the substituent R is phenyl (C3-C6) alkenoyl substituted by phenyl which may be (C1-C6) alkoxy.

More preferably, the invention relates to polypeptide compounds wherein the substituent R 1 is benzoyl substituted with isoxazolyl, which may be phenyl having (C 1 -C 6) alkoxy.

More preferably, the invention relates to polypeptide compounds wherein the substituent R 1 is -CO 2 - (cM 2) - (cH 2 tcH 3 N - 'N-O / Da), a pharmaceutically acceptable salt thereof.

The novel polypeptide compound [I] and a pharmaceutically acceptable salt thereof can be prepared by the following reaction scheme. or can be prepared by eliminating amino-1, a protecting group in R.

7

Method 1

HO OH

HO O) - (R 1 -OH

1 V-NH \ H 3 C —or its reactive derivative in the carboxy group y = 0 or a salt thereof HO / ^ ° HN OH ** V> .JK ,, H2N 0 = / ΗΟ \> “ΝΗγ ^ ΛθΗ or = \ ° H 0 HO-SO - (\ /> s HO [II] or a reactive derivative thereof in the amino group or a salt thereof HO OH HO O J- (1V-NH> h3c-y / NH_Ri, ';', ' -N \ = 0

HO / 1 ° HH OH

ΰ v> ° = H3 2 ° = y N-y.

: HO) NH / \

::: VT

jj / = K 0 H 0

HotoHy 0 / HO [I] or a salt thereof having the same meaning as above.

8

Suitable pharmaceutically acceptable salts of the target polypeptide compound [I] are the conventional non-toxic salts and may be a salt with a base or an acid addition salt such as an inorganic base, e.g. an alkali metal salt (e.g., sodium salt, potassium salt, etc.), earth ( ., calcium salt, magnesium salt, etc.), ammonium salt; a salt with an organic base, for example an organic amine salt (e.g., triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.); organic carboxylsulfonic acid addition salt (e.g., formate, acetate, trifluoroacetate, maleate, tartrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); salt with a basic or acidic amino acid (e.g., arginine, aspartic acid, glutamic acid, etc.).

In the preceding and following descriptions of this publication, suitable examples and illustrations of the various definitions included within the scope of the present invention will now be explained in detail.

The term "lower" is used to mean a group of 1 to 6 carbon atoms, unless otherwise stated.

The term "upper" is used to mean a group of 7-20 carbon-l1 atoms unless otherwise stated.

A suitable example of the term "one or more" may be a number: 1-6, of which the number 1-3 may be preferred.

A suitable example of the term "lower alkanoyl" may be straight or branched such as formyl, acetyl, 2-methylacetyl, 2,2-dimethylacetyl, propionyl, butyryl, isobutyryl, pentanoyl-1,1', 2,2-dimethylpropionyl, hexanoyl and the like.

A suitable example of the term "lower alkoxy" may be straight or branched, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, neo-pentyloxy, hexyloxy, isohexyloxy and the like, of which h is preferred may be methoxy, ethoxy, propoxy, butoxy, pentyloxy,, h! hexyloxy and isohexyloxy.

A suitable example of the term "higher alkoxy" may be straight or branched, such as heptyloxy, octyloxy, 3,5-dimethyloxyloxy, 9,7,7-dimethyloxyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, hexadecyloxy, heptadecyloxy, icyloxy and the like, of which C7-C14) alkoxy may be preferred, and even more preferred may be heptyloxy and octyloxy.

A suitable example of the term "lower alkyl" may be straight or branched having from 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-pentyl, neo- pentyl, hexyl, isohexyl and the like, of which methyl, pentyl, hexyl and isohexyl may be preferred.

A suitable example of the term "upper alkyl" may be straight or branched having 7-20 carbon atoms such as heptyl, octyl, 3,5-dimethyloctyl, 3,7-dimethyloctyl, nonyl, Decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, icosyl and the like, of which (07-04) alkyl may be preferred, and even more preferred may be heptyl, octyl, nonyl and Decyl.

A suitable example of the term "halogen" may be fluorine, chlorine, bromine and iodine.

A suitable example of the term "lower alkenyloxy" may be vinyloxy, 1- (or 2-) propenyloxy, 1- (or 2- or 3-) butenyloxy, I '<1 - (or 2- or 3- or 4-) pentenyloxy, 1- (or 2- or 3- or 4- or 5-) hexenyloxy and the like, of which (C2-C8) alkenyloxy may be preferred, and 5-hexenyloxy may be most preferred.

A suitable example of the term "upper alkenyloxy" may be V: (C 7 -C 20) alkenyloxy, of which 6-heptenyloxy and 7-octenyloxy may be preferred.

A suitable example of the term "cyclo (lower) alkyl" may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, of which cyclo (C 4 -C 0) alkyl may be preferred, and most preferred may be. ... I cyclohexyl.

A suitable example of the term "upper alkanoyl" may be heptanoyl, h 1 octanoyl, nonanoyl, decanoyl, undecanoyl, lauroyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, hepta-decanoyl, octadecanoyl, 10 be (C7-C20) alkanoyl, and hexadecanoyl may be most preferred.

A suitable example of the term "protected amino" may be lower or higher alkoxycarbonylamino (e.g., methoxycarbonylamino, ethoxycarbonylamino, t-butoxycarbonylamino, t-pentyloxycarbonylamino, heptyloxycarbonylamino, etc.), ar (lower) alkoxy (e.g. phenyl (lower) alkoxycarbonylamino (e.g. benzyloxycarbonylamino, etc.), etc.], an amino group substituted with a conventional protecting group such as ar (lower) alkyl which may have the appropriate substituent (s) (e.g., benzyl, trityl) , etc.) and the like, of which phenyl (lower) alkoxycarbonylamino may be preferred, and benzyloxycarbonylamino may be most preferred.

The process for preparing the polypeptide compound [I] or a salt thereof which is the subject of the present invention is detailed below.

Method 1

The subject polypeptide compound [I] or a salt thereof may be prepared by reacting a compound [II] or a reactive derivative thereof at an amino group or a salt thereof with a carboxy group of a compound [III] or a reactive derivative thereof.

A suitable reactive derivative of compound [III] in the carboxy group may be an acid halide, an acid anhydride, an activated amide, an activated ester and the like. Suitable examples of reactive derivatives; it may be an acid chloride; an acid azide; mixed acid anhydride with an acid such as substituted phosphoric acid [e.g. dialkylphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid, etc.], dialkylaliphosphoric acid, sulfuric acid, propionic acid, sulfuric acid, sulfonic acid, e.g. , isobutyric acid, civic acid, pentanoic acid, isopentaenoic acid, 2-ethylbutyric acid, trichloroacetic acid, etc.] with b'1: or aromatic carboxylic acid (e.g. benzoic acid, etc.); symmetric acid anhydride; dimethylpyrazole, triazole, tetrazole or 1-hydroxy-1H-benzotriazole; or an activated ester [e.g., cyanomethyl ester, methoxymethyl ester, dimethylaminomethyl [(CH 3) 2 H = CH-] ester, vinyl ester, propargyl ester, p - 11 nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenylthio oester, p-nitrophenylthioester, p-cresylthioester, carboxymethylthioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolylthioester, etc.], or ester of N-hydroxy compound [e.g. N, N-dimethylhydroxylamine, 1-hydroxy-2- (1H) -pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole, etc.], and the like. These reactive derivatives may optionally be selected according to the compound [III] used.

Suitable salts of compound [III] and its reactive derivative may be those exemplified for the subject polypeptide compound [I].

The reaction is usually carried out in a conventional solvent such as water, alcohol [e.g. methanol, ethanol, etc.], acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N, N-dimethylformamide, pyridine or any other organic solvent which does not adversely affect the reaction. These conventional solvents may also be used in admixture with water.

When the compound [III] is used in this reaction in the free acid form or in the form of a salt thereof, the reaction is preferably carried out with a conventional condensing agent such as N, N 1 -dicyclohexylcarbodiimide; N-cyclohexyl-N'-morpholinoethylcarbodiimide-imide; N-cyclohexyl-N '- (4-diethylaminocyclohexyl) carbodiimide; N, N'-11 diethylcarbodiimide, N, N'-diisopropylcarbodiimide; N-ethyl: N '- (3-dimethylaminopropyl) carbodiimide, N, N-carbonylbis- (2,'; ', methylimidazole) n; pentamethyleneketene-N-cyclohexylimine; diphenylketene-N-cyclohexylimine; ethoxyacetylene; 1-alkoxy-2-chloroethylene; trialkyl; ethyl polyphosphate; | i. isopropyl polyphosphate; phosphorus oxychloride (phosphoryl chloride); phosphorus trichloride; thionyl chloride; oxalyl; lower alpha-alkyl halogenoform [e.g. ethyl chloroformate, isopropyl chloro! roformate, etc.]; triphenylphosphine; 2-ethyl-7-hydroxy; benzisoxazolium salt; An intramolecular salt of 2-ethyl-5- (m-sulfophenyl) isoxazolium hydroxide; 1- (p-chlorobenzenesulfonamide nisulfonyylioksi) -6-chloro-lH-benzotriazole; the so-called Vilsmeier reagent prepared by reacting N, N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorus oxychloride, methanesulfonyl chloride, etc .; or the like.

12

The reaction may also be carried out on an inorganic or organic base such as an alkali metal carbonate, an alkali metal bicarbonate, a tri (lower) alkylamine, pyridine, di (lower) alkylaminopyridine (e.g. 4-dimethylaminopyridine, etc.), N- (lower) alkylmorpholine, In the presence of N-di (lower) alkylbenzylamine or the like.

The reaction temperature is not accurate and the reaction is usually carried out under cooling to heating.

The starting compound [II] is a known compound. It can be prepared by the fermen method and the synthetic methods described in EP 0462531 A2.

The culture of Coleofoma sp. F-11899 used in said fermentation process has been ordered by the National Institute of Biotechnology and Human Technology (formerly: Fermentation Research Institute of Industrial Science and Technology) (1-3, Higashi 1-chome , Tsukuba-shi, IBARAKI 305, JAPAN) on October 26, 1989 under the number FERM BP-2635.

The compounds obtained by the above method 1 may be isolated and purified by conventional methods such as powdering, recrystallization, column chromatography, high performance liquid chromatography (HPLC), reprecipitation or the like.

The compounds obtained by the above method 1 can be obtained as its hydrate, and its hydrate is within the scope of the present invention.

It will be appreciated that each of the target compounds (I) may have one or more stereoisomers such as an optical isomer and a geometric isomer depending on the asymmetric carbon atom (s) and double bond / double bond and all such isomers and mixtures are within the scope of this invention.

The biological activity of the polypeptide compounds [I] of the present invention; gical properties

To demonstrate the utility of the polypeptide compounds [I] of the present invention, the biological values of representative compounds will be described below.

13

Experiment 1 (Antimicrobial Activity): The in vitro antimicrobial activity of the test compounds described below was determined by a double agar plate dilution method.

A spoonful of overnight cultured micro-organism in Sa-bouraud broth containing 2% glucose (105 viable cells per milliliter) was stained with Sabouraud dextrose agar (SDA: dextrose 2%) containing staggered concentrations. and the minimum inhibitory concentration (MIC) was given in pg / ml after 24 hours incubation at 30 ° C.

Test organisms: C.albicans FP633

Test results

No. Compound MIC (pg / ml)

Comparison A Example 0.78 of EP-A-0462531

Comparison B Example 0.78 of EP-A-0462531 Example 45 1 Example 54 0.2 2 Example 118 0.39 3 Example 74 0.1 "4 Example 113 0.39 5 Example 82 0.39. 6 Example 81 0 , 2: · '7 Example 103 0.2 d ": 8 Example 114 0.2 9 Example 89 0.05 10 Example 112 0.1' 11 Example 51 0.1 12 Example 109 0.2; ·, 13 Example 62 0.2 i 14 Example 60 0.39 15 Example 63 0.39 .. · 16 Example 44 0.1 17 Example 50 0, 0125: 18 Example 106 0.39 19 Example 12 0.2 20 Example 13 0, 39 21 Example 45 0.2 22 Example 48 0.2 23 Example 26 0.2 14 24 Example 17 0.2 25 Example 83 0.1 26 Example 84 0.1 27 Example 21 0.1 28 Example 31 0.1 29 Example 16 0.1 30 Example 77 0.39 31 Example 20 0.1 32 Example 40 0.1 33 Example 64 0.1 34 Example 70 0.1 35 Example 25 0.05 36 Example 93 0.1 37 Example 99 0.2 38 Example 88 0.1 39 Example 102 0.39 40 Example 53 0.05 41 Example 97 0.05 42 Example 107 0.025 43 Example 24 0.1 44 Example 22 0.05 45 Example 35 0.05

It is clear from the test result that the present polypeptide compound [I] of the invention has antimicrobial activity (in particular anti-fungal activity).

: 1: The pharmaceutical composition of the present invention can be used in the form of a pharmaceutical preparation, for example as a solid, semi-solid or solution containing the polypeptide compound (I) or a pharmaceutically acceptable salt thereof as an active ingredient in admixture with a organic carrier or excipient suitable for rectal administration; pulmonary (nasal or buccal inhalation); ocular-1 '; external (topical); for oral administration; for parenteral (including subcutaneous, intravenous or intramuscular) administration; for inhalation (including metered dose inhalers); nebulaattoreissa; or dry powder hay-1 in 1L.

The active ingredient may be incorporated, for example, into conventional non-toxic pharmaceutically acceptable carriers in solid forms such as granules, tablets, troches, pellets, tablet granules, capsules or suppositories; ointments, 15 ointments; aerosols; powder for inhalation; liquid forms such as solutions, emulsions, or suspensions for injection; to nourish; eye drops; and any other form suitable for use. If necessary, stabilizers, thickeners, wetting agents, emulsifiers, and coloring agents may be included in the above additives; perfumes or buffers; or any other commonly used may be used as an additive.

The present polypeptide compound [I], or a pharmaceutically acceptable salt thereof, is / are incorporated into a pharmaceutical composition in an amount sufficient to provide the desired antimicrobial activity in the diseased process or condition.

For administration to a human, it is advisable to administer it by the intravenous, intramuscular, pulmonary, oral or inhalation routes. Although the dosage of the therapeutically effective amount of the present polypeptide compound [I] will vary and will also depend on the age and condition of the individual subject being treated, a daily dose of 0.01 to 20 mg of the present polypeptide compound [I] per kg of human body weight 1 to 20 mg of the present polypeptide compound [I] per kg of human body weight and for oral administration a daily dose of 0.5 to 50 mg of the present polypeptide compound [I] per kg of human body weight is generally mentioned in the treatment and prevention of infectious diseases.

* Particularly when treating and preventing Pneumocystis carinii infections, the following should be noted.

; When administered by inhalation, the compounds of the present invention are best administered in aerosol spray form as pressurized powders which can be formulated and powder mixtures can be inhaled using a powder inhaler device. The most popular an-! The delivery system for inhalation is a metered dose, inhalation aerosol that may be formulated as a suspension of the compound or as a solution in a suitable propellant such as hydrofluorocarbons or hydrocarbons.

Since direct application to the lungs and bronchi is advisable, the route of administration of the aerosol is the preferred method of administration. Inhalation is also a recommended method, especially if the infection may spread to the ears and other body cavities.

Alternatively, parenteral administration may also be effected using an intravenous drip dose.

The following preparations and examples are provided to further illustrate the present invention.

Preparation 1

To a suspension of 1- (4-hydroxyphenyl) -4-tert-butoxycarbonylpiperazine (3 g) and potassium carbonate (0.82 g) in N, N-dimethylformamide (15 ml) was added octyl bromide (1.87 ml). The mixture was stirred for 10 hours at 70 ° C. The reaction mixture was added to a mixture of water and ethyl acetate. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted (hexane: ethyl acetate = 9: 1). The fractions containing the target compound were combined and evaporated under reduced pressure to give 1- (4-n-octyloxyphenyl) -4-tert-butoxycarbonylpiperazine (2.71 g). IR (KBr): 1687, 1513, 1241 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.2Hz), 1.2-1.4 (10H, m), 48 (9H, s), 1.65-1.85 (2H, m), 3.00 (4H, t, J = 5.2Hz), 3.57 (4H, t, J = 5.2Hz), 3.90 (2H, t, J = 6.5Hz), 6.83 (2H, dd, J = 6.4 and 2.1Hz), 6.89 (2H, dd, J = 6.4 and 2, 1 Hz)

Preparation 2 '1 A solution of 1- (4-n-octyloxyphenyl) -4-tert-butoxy-carbonylpiperazine (2.61 g) in trifluoroacetic acid (20 ml) was stirred for 4 hours at ambient temperature. The reaction mixture was evaporated under reduced pressure and to the residue was added a mixture of 1N aqueous NaOH and ethyl acetate. The organic layer was separated and V dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure to give 1- (4-n-octyloxyphenyl) piperazine (0.86 g).

IR (KBr): 2923, 1513, 1259, 831 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.4Hz), 1.2-1.53 (10H, m), 65-1, 85 (2H, m), 3.03 (4H, s), 3.90 (2H, t, J = 6.5Hz), 6.83 (2H, dd, J = 6.4 and 2 , 9Hz), 6.90 (2H, dd, J = 6.4 and 2.9Hz) APCI MASS: m / z = 291 (M + +1)

Preparation 3

A suspension of 1- (4-n-octyloxyphenyl) piperazine (1 g) and potassium carbonate (0.476 g) in N, N-dimethylformamide (1 ml) was charged with p-fluorobenzonitrile (0.347 g) and stirred for 5 hours at 160 ° C. :in. The reaction mixture was added to a mixture of water and ethyl acetate. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure to give 4- [4- (4-n-octyloxyphenyl) piperazin-1-yl] benzonitrile (0.93 g).

IR (KBr): 2848, 2217, 1604, 1511, 1241 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.53 (10H, m) ), 1.65-1.85 (2H, m), 3.20 (4H, t, J = 5.4Hz), 3.48 (4H, t, J = 5.4Hz), 3.91 (2H) , t, J = 6.5Hz), 6.8-7.0 (6H, m), 7.52 (2H, d, J = 8.9Hz) APCI MASS: m / z = 392 (M ++ l)

Preparation 4

A mixture of 2,4-dihydroxybenzaldehyde (5.52 g), potassium carbonate (6.08 g) and octyl bromide (7.73 g) in acetonitrile (55 ml) was stirred for 16 hours at 60 ° C. The reaction mixture solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted (hexane: ethyl acetate = 9: 1) to give 2-hydroxy-4-octyloxybenzaldehyde (6.73 g).

NMR (CDCl 3, δ): 0.89 (3H, t, J = 8.8Hz), 1.2-1.5 (10H, m), 1.8-2.0 (2H, m), 4 0-4.2 (2H, m), 6.42 (1H, s), 6.52 (1H, d, J = 8.7Hz), 7.79 (1H, d, J = 8.7Hz) ), 10.33 (1H, s) APCI MASS: m / z = 257 (M + +1).

The following compound was obtained in the same manner as Preparation 4.

Preparation 5:; Methyl 3,4-dipentyloxy-benzoate NMR (CDCl 3, δ): 0.93 (6H, t, J = 6.0 and 9.0Hz), 1.3-2.0 (12H, m), 3.88 ( 3H, s), 4.04 (4H, m), 6.86 (1H, d, J = 8.4Hz), 7.53 (1H, d, J = 2.0Hz), 7.63 (1H, dd, J = 8.4 and 2.0 Hz) APCI MASS: m / z = 309 (M + +1) - Preparation 6

A mixture of 4-bromo-4'-pentylbiphenyl (5.04 g), trimethylsilylacetylene (2.4 ml), tetrakis (triphenylphosphine) palladium (0.96 g), triphenylphosphine (0.22 g) and copper iodide (95 mg) in piperidine (10 mL) was heated under nitrogen at 90 ° C for one hour. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and the pH was adjusted to about 16N with hydrochloric acid. The separated organic layer was washed with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure to give crude 2- [4- (4-pentylphenyl) phenyl] -1-trimethylsilylacetylene, which was used for the next reaction without further purification. The crude mixture was dissolved in a mixture of dichloromethane (10 mL) and methanol (10 mL) and potassium carbonate (2.75 g) was added at 0 ° C. The mixture was allowed to warm to ambient temperature and stirred for a further 2 hours. The reaction mixture was poured into a mixture of cold water and ethyl acetate and the resulting precipitate was filtered off. The filtrate was adjusted to pH 7 with hydrochloric acid and washed with brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude powder, which was subjected to column chromatography on silica gel (300 mL) and eluted with n-hexane: ethyl acetate = 99: 1 to 97: 3, v / v). pentylphenyl) phenylacetylene (2.09 g) · IR (Nujol): 3274, 1490 cm -1 · * · NMR (CDCl 3, δ): 0.90 (3H, t, J = 6, 4Hz), 1, 30- 1.50 (4H, m), 1.50-1.80 (2H, m), 2.64 (2H, t, J = 7.6Hz), 7.20-7.30 (2H, m), 7.45-7.60 (6H, m): 7 APCI MASS: m / z = 281 (M + + 1 + MeOH)

The following compound was obtained in the same manner as Preparation 6.

Preparation 7h · 6-Heptyloxynaphthalen-2-yl-acetylene NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.20-1, 60 (8H, m), 70-1.90 Ί (2H, m), 3.10 (1H, s), 4.07 (2H, t, J = 6.5Hz), 7.08 (1H, d, J = 2.5Hz) , 7.15 (1H, dd, J = 2.5 and 8.9Hz), 7.47 (1H, dd, J = 1.6 and 8.5Hz), 7.64 i; 3 (1H, d, J = 7.3Hz), 7.68 (1H, d, J = 8.5Hz), 7.94 (1H, d, J = 1.6Hz) APCI MASS: m / z = 267 (M + +1). Preparation 8

To a solution of 4- (4-pentylphenyl) phenylacetylene (2.09 g) in tetrahydrofuran (30 mL) was added dropwise a solution of 19 lithium diisobutylamide in a mixture of tetrahydrofuran and n-hexane (1.60 M, 5.6 mL). At -75 ° C, and the resulting mixture was stirred for 1 hour at -78 ° C. Methyl chloroformate (0.72 mL) was added and the reaction mixture was allowed to warm to ambient temperature. The solution was diluted with ethyl acetate and washed alternately with water and brine and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give the crude product which was subjected to column chromatography on silica gel (150 mL) and eluted with a mixture (n-hexane: ethyl acetate = 100: 0-9: 1, v / v) to give methyl -3- [4- (4-pentylphenyl) phenyl] propionate (2.20 g).

IR (Nujol): 2225, 1712 cm -1 * - NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.25-1.50 (4H, m), 52-1.80 (2H, m), 2.64 (2H, t, J = 7.6Hz), 3.85 (3H, s), 7.20-7.35 (2H, m), 7, 40.-7.70 (6H, m) APC1 MASS: m / z = 307 (M + +1).

The following compound was obtained in the same manner as Preparation 8.

Preparation 9

Methyl 3- (6-heptyloxynaphthalen-2-yl) -propionate IR (Nujol): 2219, 1704, 1621 [delta] &lt; 1 &gt; H NMR (CDCl3, [delta]): 0.90 (3H, t, J = 6.5Hz), 1.20 -1.60 (8H, m), 1.70-2.00 δ 1 (2H, m), 3.86 (3H, s), 4.08 (2H, t, J = 6.5Hz), 7 , 10 (1H, d, J = 2.5Hz), 7.17 (1H, dd, J = 2.5 and 8.9Hz), 7.52 (1H, dd, J = 1.6 and 8.5Hz) ), 7.68: v, (1H, d, J = 7.3Hz), 7.72 (1H, d, J = 8.5Hz), 8.06 (1H, d, J = 1.6Hz), APCI MASS: m / z = 325 (M + +1) &lt; 1 &gt;

A mixture of 4-bromo-4'-pentylbiphenyl (5.0 g), methyl acrylate (2.2 ml), palladium acetate (0.11 g) and tris (o-to-"yl) phosphine (O) was added. 60 g) in triethylamine (16 ml) was refluxed for 15 hours under a nitrogen atmosphere.

water and ethyl acetate, and the pH was adjusted to about 1.5 6N

hydrochloric acid. The separated organic layer was washed alternately with water and brine, and dried over magnesium sulfate. la. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude powder which was columnar; was chromatographed on silica gel (200 mL) and eluted with a mixture of (n-hexane: ethyl acetate = 100: 0 to 94: 6, v / v) to give methyl 3- [4- (4-pentylphenyl) phenyl] acrylate (4). , 48 g).

20 IR (Nujol): 1718, 1637 cm -1 NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.7Hz), 1.20-1.50 (4H, m), 1 , 50-1.80 (2H, m), 2.65 (2H, t, J = 7.4Hz), 3.82 (3H, s), 6.47 (1H, d, J = 16.0Hz) , 7.20-7.35 (2H, m), 7.45-7.68 (6H, m), 7.73 (1H, d, J = 16.0Hz) APCI MASS: m / z = 309 (M ++ 1)

The following compounds (Preparations 11-1-3) were obtained in the same manner as Preparation 10.

Preparation 11

Methyl 3- (6-heptyloxynaphthalen-2-yl) acrylate IR (Nujoli): 1716, 1625, 1459 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1 , 20-1.65 (8H, m), 1.76-1.93 (2H, m), 3.82 (3H, s), 4.07 (2H, t, J = 6.5Hz), 6 , 49 (1H, d, J = 16.0Hz), 7.05-7.20 (2H, m), 7.55-7.90 (5H, m) APCI-MS: m / z = 327 (M ++ 1)

Preparation 12

Methyl 3- [4- (4-heptyl-phenyl) -phenyl] -acrylate NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.5Hz), 1.15-1.50 (8H, m ), 1.50-1.75; (2H, m), 2.64 (2H, t, J = 7.6Hz), 3.81 (3H, s), 6.46 (1H, d, J = 16.0Hz), 7.26 (2H , d, J = 8.2Hz), 7.52 (2H, d, J = 8.2Hz), 7.59 (6H, J: s), 7.73 (1H, d, J = 16.0Hz) ) I ': APCI MASS: m / z = 337 (M ++ 1)

Preparation 13 1 Methyl 3- [4- (4-pentyloxy-phenyl) -phenyl] -acrylate NMR (CDCl 3, δ): 0.94 (3H, t, J = 7.0Hz), 1.30-1.60 (4H, m), 1.70-1.93 (2H, m), 3.82 (3H, s), 4.00 (2H, t, J = 6.7Hz), 6.45 (1H, d, J = 16.0Hz), 6.90-7.05 (2H, m), 7.48-8.65 (6H, m), 7.72 (1H, d, J = 16.0Hz). m / z = 325 (M + +1) .. ·: Preparation 14 '1' A mixture of 6-heptyloxynaphthalene-2-carboxylic acid (1.00 µg) and thionyl chloride (5 ml) was stirred for 18 hours at ambient temperature. and concentrated under reduced pressure to give crude 6-heptyloxy-2-naphthoyl chloride. To a mixture of ethyl isonic pecotinate (605 mg), triethylamine (425 mg) and N, N → 21 dimethylaminopyridine (10 mg) in dichloromethane (10 ml) was added crude 6-heptyloxy-2-naphthoyl chloride and the mixture was stirred for 2 hours at ambient temperature. and diluted with dichloromethane. The mixture was washed with water, 1N hydrochloric acid and brine and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted (n-hexane: ethyl acetate = 3: 1) to give 4-ethoxycarbonyl-1- (6-heptyloxy-2-naphthoyl) piperidine (1.20 g).

NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.6Hz), 1.2-2.0 (19H, m), 2.5-2.7 (1H, m), 3, 0-3.2 (2H, m), 4.1-4.3 (4H, m), 7.1-7.2 (2H, m), 7.44 (1H, dd, J = 8.4 and 1.7Hz), 7.72 (1H, d, J = 3.9Hz), 7.77 (1H, d, J = 3.9Hz), 7.82 (1H, s) APCI MASS: m / z = 426 (M ++ 1)

Preparation 15

To a mixture of methyl 3,4-diaminobenzoate (1.91 g) and triethylamine (0.56 g) in N, N-dimethylformamide (20 mL) was added decanoyl chloride (2.31 g), and the mixture was stirred for one hour. 0 ° C. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure. The residue was dissolved in methanol (20 mL) and concentrated. sulfuric acid (0.05 ml) was added, and. . the mixture was stirred for 6 hours at 60 ° C. After cooling, the reaction mixture was evaporated under reduced pressure. The residue was diluted with ethyl acetate; (tat and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel eluting with 3: ) gave 5-methoxycarbonyl-2-nonylbenzimidazole (1.40 g).

IR (KBr pellet): 2923, 1718, 1623, 1544, 1438, 1413, 1288, 1213, t1 (1085/750 cm -1); 1 H NMR (DMSO-d 6, δ): 0.84 (3H, t, J = 6.7Hz), 1.1-1.4 (12H, m), 1.7-1.9 (2H, m), 2.83 (2H, t, J = 7, 4Hz), 7.56 (1H, d, J = 8.4Hz), 7.78 (1H, d, J = 8.4Hz), 8.07 (1H, s) APCI MASS: m / z = 303 (M ++ 1): 1,: Preparation 16

To a mixture of dimethyl malonate (4 ml), 2-hydroxy-4-octyloxybenzaldehyde (2.50 g) and piperidine (0.1 ml) in methanol (10 ml) was added acetic acid (0.01 ml), and was stirred for 3 hours at 70 ° C. The solvents were removed under reduced pressure, and the residue was dissolved in ethyl acetate and washed with 0.5N hydrochloric acid, water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure and the precipitate was collected by filtration and washed with n-hexane and dried to give methyl 7-octyloxycoumarin-3-carboxylate (0.94 g).

NMR (DMSO-d6, δ): 0.86 (3H, m), 1.2-1.6 (10H, m), 1.7-1.8 (2H, m), 3.81 (3H, s), 4.11 (2H, t, J = 6.4Hz), 6.9-7.1 (2H, m), 7.83 (1H, d, J = 9.0Hz), 8.75 ( 1H, s) APCI MASS: m / z = 333 (M + +1).

Preparation 17

To a mixture of sodium hydride (423 mg) and 4-octylphenol (2.06 g) in tetrahydrofuran (16 ml) was added ethyl 2-chloroacetoacetate dropwise at ambient temperature. The mixture was stirred for 6 hours at 70 ° C under a nitrogen atmosphere and poured into a saturated aqueous solution of ammonium chloride. The solution was extracted with ethyl acetate and the organic layer was washed with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure. The residue was added conc. E 2 SO 4 (10 mL) at 0 ° C and the mixture was stirred for 10 minutes.

The reaction mixture was poured into ice water and the pH was adjusted to 7.0 with 1N aqueous NaOH and extracted with ethyl acetate. The organic layer was washed with water and brine and dried over magnesium sulfate. The magnesium sulfate was filtered off with a filter '', and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted (hexane: ethyl acetate = 95: 5). The fractions containing the target compound were combined and evaporated under reduced pressure to give ethyl 3-methyl-5-octyl-benzo [b] furan-2-carboxylate (1.44 g).

IR (neat): 2925, 2854, 1712, 1596, 1463, 1292, 1149, 1089 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.7Hz), 1.2-1 , Δ (10H, m), 1.44 (3H,?: T, J = 7, 1Hz), 1.6-1.8 (2H, m), 2.58 (3H, s), 2.71 (2H, t, J = 8.0Hz), δ: 4.45 (2H, t, J = 7.1Hz), 7.2-7.5 (3H, m) APCI MASS: m / z = 317 (M ++ 1). ': Preparation 18

To a solution of ethyl 3-amino-4-hydroxybenzoate (1.81 g) 23 and triethylamine (1.53 ml) in dichloromethane (20 ml) was added dropwise decanoyl chloride (2.01 ml) at 0 ° C. The reaction mixture was stirred for 48 hours at ambient temperature and washed with water, 0.5N hydrochloric acid, water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure. To a residue dissolved in xylene (30 mL) was added p-toluenesulfonic acid monohydrate (0.5 g) and the mixture was stirred for 4 hours at 130 ° C. Ethyl acetate was added to the mixture and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel (n-hexane: ethyl acetate = 9: 1, v / v) gave ethyl 2-nonylbenzo [b] oxazole-6-carboxylate (2.36 g).

IR (KBr pellet): 2914, 1722, 1621, 1575, 1470, 1429, 1365, 1290, 1203, 1151, 1115, 1081, 1022 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.7Hz), 1.2-1.4 (12H, m), 1.42 (3H, t, J = 7.2Hz), 1.90 (2H, m), 2.95 (2H, t) J = 7.4Hz), 4.40 (2H, q, J = 7.0Hz), 7.50 (1H, d, J = 8.5Hz), 8.06 (1H, d, J = 8.5Hz) ), 8.37 (1H, s) APCI MASS: m / z = 318 (M + +1).

Preparation 19; A mixture of methyl 3,4-diaminobenzoate (1.84 g) and 4-hexyloxybenzaldehyde (2.30 g) in nitrobenzene (40 mL) was stirred for 48 hours at 145 ° C. After cooling, the mixture was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1) gave a 5: 1; 1-methoxycarbonyl-2- (4-hexyloxyphenyl) benzimidazole (1.19 g) · 1 H NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.4Hz), 1.2-1, 9 (8H, m), 3.92 (3H, s), 3.90-4.1 (2H, m), 6.93 (2H, d, J = 8.9Hz), 7.5-7, Δ (1H, lev), 7.94: δ (1H, dd, J = 8.5 and 1.5Hz), 8.03 (1H, d, J = 8.9Hz), 8.2-8, 4 (1H, lev): ": APCI MASS: m / z = 353 (M + +1)

Preparation 20

A mixture of methyl 3- [4- (4-pentylphenyl) phenyl] acrylate (2.0 g) and 10% palladium on carbon (50% wet, 0.2 g) in tetrahydrofuran (20 mL) ) was stirred for 8 hours under hydrogen atmosphere at ambient temperature. The catalyst was filtered off and the filtrate was evaporated under reduced pressure to give methyl 3- [4- (4-24 pentylphenyl) phenyl] propionate (1.93 g).

NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.8Hz), 1.25-1.50 (4H, m), 1.50-1.75 (2H, m), 2, 55-2.75 (4H, m), 2.99 (2H, t, J = 8.0Hz), 3.68 (3H, s), 7.10-7.30 (4H, m), 7, 40.-7.60 (4H, m) APCI MASS: m / z = 311 (M + +1).

Preparation 21

A mixture of methyl 3- [4- (4-pentyloxyphenyl) phenyl] acrylate (2.70 g) and platinum oxide (0.41 g) in tetrahydrofuran (40 ml) was stirred for 8 hours under 3 hydrogen at ambient temperature. The catalyst was filtered off and the filtrate was evaporated under reduced pressure to give methyl 3- [4- (4-pentyloxyphenyl) phenyl] propionate (2.70 g).

NMR (CDCl 3, δ): 0.94 (3H, t, J = 7.0Hz), 1.28-1.60 (4H, m), 1.60-1.95 (2H, m), 2, 55-2.78 (2H, m), 2.98 (2H, t, J = 7.8Hz), 3.98 (2H, t, J = 6.5Hz), 6.85-7.05 (2H) , m), 7.05-7.30 (2H, m), 7.40-7.55 (4H, m) APCI MASS: m / z = 327 (M + +1).

The following compound was obtained in the same manner as Preparation 21.

Preparation 22

Methyl 3- (6-heptyloxynaphthalen-2-yl) propionate NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.20-1.70 (8H, m), 1 , 70-1.93 (2H, m), 2.70 (2H, t, J = 7.7Hz), 3.07 (2H, t, J = 7.7Hz), 3.67 (3H, s) ,; v 4.05 (2H, t, J = 6.5Hz), 7.02-7.20 (2H, m), 7.20-7.38 (2H, m), 7.55: ( 1H, s), 7.66 (1H, dd, J = 3.0 and 8.5Hz) 1 APCI MASS: m / z = 329 (M + +1)

Preparation 23

To a mixture of methyl 3- [4- (4-pentylphenyl) phenyl]: acrylate (0.41 g) in tetrahydrofuran (5 ml) was added 3N NaOH: aqueous solution (1.3 ml) and the resulting mixture was heated to 85 ° C. To C for 10 hours, thia. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and the pH was adjusted to about 2.6N hydrochloric acid, h ": The separated organic layer was washed alternately with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, under pressure to give 3- [4- (4-pentylphenyl) phenyl] acrylic acid (0.41 g).

NMR (DMSO-d6, δ): 0.87 (3H, t, J = 7.5Hz), 1.15-1.46 (4H, m), 1.48- 1.70 (2H, m) , 2.61 (2H, t, J = 7.4Hz), 6.56 (1H, d, J = 16.0Hz), 7.29 (2H, d, J = 8.2Hz), 7.60 ( 2H, d, J = 4.0Hz), 7.66 (2H, d, J = 4.0Hz), 7.68-7.85 (3H, m) APCI MASS: m / z = 295 (M + + S)

The following compounds (Preparations 24 to 31J) were obtained in the same manner as Preparation 23.

Preparation 24 3- [4- (4-Pentyloxy-phenyl) -phenyl] -propionic acid IR (Nujol): 1697, 1606, 1500 cm -1 NMR (CDCl 3, δ): 0.94 (3H, t, J = 7.1 Hz), 1.25-1.60 (4H, m), 1.70-1.95 (2H, m), 2.72 (2H, t, J = 7.5Hz), 3.00 (2H, t, J) = 7.5Hz), 3.99 (2H, t, J = 6.5Hz), 6.95 (2H, dd, J = 2.1, and 6.7Hz), 7.25 (2H, d, J = 8.2Hz), 7.40-7.60 (4H, m) APCI MASS: m / z = 313 (M + +1)

Preparation 25 3- [4- (4-Heptylphenyl) phenyl] propionic acid MR (CDCl 3, δ): 0.88 (3H, t, J = 6.8Hz), 1.15-1.50 (8H, m), 1.50-1.78 (2H, m), 2.65 (2H, t, J = 7.6Hz), 6.48 (1H, d, J = 16.0Hz), 7.27 (2H, d) , J = 8.2Hz), 7.53 (2H, d, J = 8.2Hz), 7.63 (4H, m), 7.83 (1H, d, J '- J = 16.0Hz) APCI MASS: m / z = 323 (M + +1)

Preparation 26 * '3- [4- (4-Pentylphenyl) phenyl] propionic acid / 1'; NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.4Hz), 1.20-1.50 (4H, m), 1.50-1.75 (2H, m), 2, 64 (2H, t, J = 8.0Hz), 2.67 (2H, t, J = 9.6Hz), 3.00 (2H, t, J = 8.0Hz), 7.15-7.38 (4H, m), 7.38-7.60 (4H, m) APCI MASS: m / z = 297 (M + +1) ", Preparation 27, 1,3- (6-Heptyloxynaphthalene-2- yl) propionic acid NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.20-1.65 (8H, m), 1.75-2.00 '(2H, m) ), 2.75 (2H, t, J = 7.7Hz), 3.09 (2H, t, J = 7.7Hz), 4.06 (2H, t, J = 6.5Hz), 7.05 -7.15 (2H, m), 7.15-7.35 (2H, m), 7.50-7.73 (2H, m) APCI-MASS: m / z = 315 (M + +1). 26

Preparation 28 3- (6-Heptyloxynaphthalen-2-yl) acrylic acid NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.15-1.60 (8H, m), 1 , 75-1.95 (2H, m), 4.09 (2H, t, J = 6.5Hz), 6.51 (1H, d, J = 16.0Hz), 7.09-7.30 ( 2H, m), 7, 65-8, 00 (5H, m)

Preparation 29 3- [4- (4-Pentylphenyl) phenyl] propionic acid NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.5Hz), 1.23-1.50 (4H, m), 1.50-1.80 (2H, m), 2.65 (2H, t, J = 7.6Hz), 7.27 (2H, d, J = 8.2Hz), 7.51 (2H, d) , J = 8.2Hz), 7.58-7.80 (4H, m) APCI MASS: m / z = 325 (M + +1 + MeOH)

Preparation 30 3- (6-Heptyloxynaphthalen-2-yl) -propionic acid IR (Nujol): 2645, 2198, 1670, 1627 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6, 5Hz), 1.10-1.60 (8H, m), 1.65-1.90 (2H, m), 4.10 (2H, t, J = 6.5Hz), 7.24 (1H, dd, J = 2.4 and 8.9Hz), 7.39 (1H, d, J = 2.5Hz), 7.55 (1H, dd, J = 1.6 and 8.5Hz), 7.8 -8.0 (2H, m), 8.22 (1H, d, J = 1.6Hz) APCI MASS: m / z = 343 (M + +1 + MeOH): Preparation 31 4- [5- ( 4-Pentyloxy-phenyl) -isoxazolyl-3-yl] -benzoic acid IR (KBr): 2939, 2867, 1681, 1614, 1429, 1255, 1178, 821 cm-1:: NMR (DMSO-d6, δ): 0.91 (3H, t, J = 7.1 Hz), 1.3-1.5 (4H, m), 1.6-1.8 (2H, m), 4.04 (2H, t, J = 6, 5Hz), 7.11 (2H, d, J = 8.9Hz), 7.54 (1H, s), 7.85 (2H, d, J = 8.9Hz), 7.98 (2H, d, J = 8.6Hz), 8.11 (2H, d, J = 8.6Hz) APCI MASS: m / z = 352 (M + H) +;

To a solution of ethyl 3-methyl-5-octylbenzo [b] furan-2-carboxylate (1.44 g) in ethanol (20 ml) was added 10% aqueous NaOI-I (2.2 ml) and was stirred for 2 hours at ambient temperature and evaporated under reduced pressure. The pH of the residue was adjusted to 3.0 with hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The magnesium sulfate was separated by filtration and the filtrate evaporated under reduced pressure to give 3-methyl-5-octylbenzo [b] furan-2-carboxylic acid (1.00 g).

IR (KBr pellet): 2923, 1689, 1664, 1581, 1456, 1319, 1159, 933 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.7Hz), 1 , 2-1.5 (10H, m), 1.5-1.8 (2H, m), 2.49 (3H, s), 2.69 (2H, t, J = 7.9Hz), 7 , 32 (1H, dd, J = 8.5 and 1.7Hz), 7.52 (1H, d, J = 8.5Hz), 7.54 (1H, d, J = 1.7Hz), 13, 2-13.5 (1H, lev) APCI MASS: m / z = 289 (M ++ 1)

The following compounds (Preparations 33-3-9) were obtained in the same manner as Preparation 32.

Preparation 33 3,4-Dipentyloxy-benzoic acid NMR (DMSO-d6, δ): 0.89 (6H, t, J = 6.8Hz), 1.2-1.5 (8H, m), 1.6-1, Δ (4H, m), 3.9-4.1 (4H, m), 7.02 (1H, d, J = 8.4Hz), 7.43 (1H, d, J = 1.7Hz), 7.53 (1H, dd, J = 8.4 and 1.7Hz) APCI MASS: m / z = 295 (M + +1).

Preparation 34 1- (6-Heptyloxy-2-naphthoyl) piperidine-4-carboxylic acid; NMR (DMSO-d6, δ): 0.88 (3H, t, J = 6.7Hz), 1.2-2.0 (14H, m), 2.5-2.6: (1H, m) , 2.9-3.2 (2H, lev), 3.25 (2H, s), 4.09 (2H, t, J = 6.5Hz), δ; 7.20 (1H, dd, J = 8.9 and 2.4Hz), 7.36 (1H, d, J = 2.3Hz), 7.43 (1H, dd, J = 8, 4 and 1, 5Hz), 7.8-8.0 (3H, m), 12.30 (1H, lev), APCI-MASS: m / z = 398 (M + + 1):; Preparation 35 "7-Octyloxycoumarin-3-carboxylic acid" IR (KBr): 1748, 1625, 1558, 1467, 1430, 1386, 1360, 1257, 1217, 1120 '. Cm -1.' NMR (DMSO-d , δ): 0.86 (3H, t, J = 6.8Hz), 1.2-1.5 (10H, m), 1.6-1.8 (2H, m), 4.11 (2H) , t, J = 6.4Hz), 6.9-7.1 (2H, m), 7.82 (1H, d, J = 8.9Hz), 8.72 (1H, s), 12 , 98 (1H, lev),; 'APCI MASS: m / z = 319 (M + +1).

Preparation 36 4- (4-Pentyloxyphenyl) cinnamic acid 28 IR (Nujol): 2923, 1675, 1500, 1290, 1223, 985, 821 cm-1 NMR (DMSO-d6, δ): 0.90 (3H, t, J = 7.0Hz), 1.3-1.5 (4H, m), 1.6-1.8 (2H, m), 4.01 (2H, t, J = 6.5Hz), 6.54 ( 1H, d, J = 16.0Hz), 7.02 (2H, d, J = 8.8Hz), 7.5-7.8 (7H, m) APCI MASS: m / z = 311 (M + +1)

Preparation 37 2-Nonylbenzoxazole-6-carboxylic acid NMR (DMSO-d6, δ): 0.84 (3H, t, J = 6.7Hz), 1.2-1.5 (12H, m), 1.7-. 1.9 (2H, m), 2.96 (2H, t, J = 7.4Hz), 7.76 (1H, d, J = 8.4Hz), 7.98 (1H, d, J = 8) , 4Hz), 8.19 (1H, s) APCI MASS: m / z = 290 (M + +1).

Preparation 38 2- (4-Hexyloxyphenyl) benzimidazole-5-carboxylic acid NMR (DMSO-d6, δ): 0.8-1.0 (3H, m), 1.3-1.6 (6H, m), 1 , 7-1.8 (2H, m), 4.06 (2H, t, J = 6.4Hz), 7.12 (2H, d, J = 8.8Hz), 7.6-7.9 ( 2H, m), 8.1-8.2 (3H, m), 13.00 (1H, lev) APCI MASS: m / z = 339 (M + +1).

Preparation 39 2-Nonylbenzimidazole-5-carboxylic acid V; NMR (DMSO-d6, δ): 0.85 (3H, t, J = 6.7Hz), 1.1-1.4 (12H, m), 2.7-2.9 (2H, m), 2.96 (2H, t, J = 7.6Hz), 3.6-5.2 (1H, lev), 7.66 (1H, d, J = 8.4Hz), 7.90 (1H, d) , J = 8.4Hz), 8.15 (1H, s) APCI MASS: m / z = 289 (M + + 1) < 1 &gt; Preparation 40 f. Solution of 4- [4- (4-octyloxyphenyl) piperazin-1- ... yl] benzonitrile (0.5 g) in 20% aqueous NaOH (30 mL) and acetic acid (20 mL) was refluxed for 9 hours. The reaction mixture was made:; 'powdered with water. The precipitate was collected by filtration and added to a mixture of water, tetrahydrofuran and ethyl acetate, and the pH was adjusted to 2.5 with 1N aqueous NaOH. The organic layer was separated and dried over magnesium sulfate. MAG! the sodium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4- [4- (4-octyloxyphenyl) piperazin-1-yl] benzoic acid (388 mg).

IR (KBr): 2929, 1664, 1600, 1510, 1240 cm -1 29 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.6Hz), 1.2-1.5 ( 10H, m), 1.5-1.8 (2H, m), 3.13 (4H, t, J = 5.3Hz), 3.44 (4H, t, J = 5.3Hz), 3, 88 (2H, t, J = 6.5Hz), 6.83 (2H, d, J = 9.2Hz), 6.94 (2H, d, J = 9.2Hz), 7.02 (2H, d) , J = 9.0Hz), 7.79 (2H, d, J = 9.0Hz) APCI MASS: m / z = 411 (M + +1)

Preparation 41

To a suspension of sodium hydride (60% suspension in mineral oil) (0.296 g) in N, N-dimethylformamide (14 mL) was added 1,2,4-triazole (0.511 g) and 4- [4- (8-bromooctyloxy) - phenyl] benzoic acid (1 g), and stirred for 5 hours at 120 ° C. The re-reaction mixture was added to a mixture of water and ethyl acetate and the pH was adjusted to 2.5 conc. hydrochloric acid. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4- [4- [8- (1,2,4-triazol-1-yl) octyloxy] phenyl] benzoic acid (0.81 g).

IR (KBr): 2940, 1689, 1604, 1297, 1189 cm -1 NMR (DMSO-d 6, δ): 1.1-1.53 (8H, m), 1.6-1.9 (4H, m) ), 4.00 (2H, t, J = 6.3Hz), 4.16 (2H, t, J = 7.0Hz), 7.03 (2H, d, J = 8.7Hz), 7.67 (2H, d, J = 8.7Hz), 7.75 (2H, d, J = 8.4Hz), 7.95 (1H, s), 7.99 (2H, d, J = 8.4Hz) , 8.51 (1H, s), 12.9 (1H, s) APCI MASS: m / z = 394 (M + +1); ';'; Preparation 42 '/ A mixture of 2-carbamoyl-5-methoxybenzo [b] thiophene (2.0 g), acetic acid (5 ml) and 48% hydrobromic acid (20 ml) was stirred for 16 hours at 110 ° C. , and the mixture was poured into ice water. The resulting precipitate was collected by filtration and dried to give 5-hydroxybenzo [b] thiophene-2-carboxylic acid (1.66 g).

NMR (DMSO-d6, δ): 7.03 (1H, dd, J = 8.8 and 0.6Hz), 7.31 (1H, d, J = 0.6Hz), 7.81 (1H, d, J = 8.8Hz, 7.96 (1H, s), 9.64 (1H, s), 13.32 (1H, s), APCI MASS: m / z = 195 (M + +1). )

Preparation 43 '', A solution of (S) -2-tert-butoxycarbonyl-1,2,3,4-tetrahydro-7,7-hydroxyisoquinoline-3-carboxylic acid (1 g) in a mixture of 10% NaOH: aqueous solution (2.73 mL) and dimethyl sulfoxide (11 mL) were stirred for half an hour at 80 ° C. Octyl bromide (0.589 ml) was then added thereto and stirred for 4 hours at 60 ° C. The reaction mixture was added to a mixture of water and ethyl acetate and the pH was adjusted to 2.5 conc. hydrochloric acid. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure to give (S) -2-tert-butoxycarbonyl-1,2,3,4-tetrahydro-7-octyloxy-isoquinoline-3-carboxylic acid (1.30 g).

IR (neat): 2929, 1743, 1704, 1164 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6, 1Hz), 1.1-1.6 (10H, m), 1.41 + 1.51 (9H, s, cis + trans), 1.75 (2H, Quint, J = 6.5Hz), 3.10 (2H, m), 3.90 (2H, t, J = 3.9Hz), 4.42 (1H, d, J = 16.8Hz), 4.65 (1H, d, J = 16.8Hz), 4.74 + 5.09 (1H, m, cis + trans), 6.5-6.8 (2H, m), 7.03 (1H, d, J = 8.3Hz) APCI MASS: m / z = 306 (M + +1-Boc)

The following compounds (Preparations 44 - 4-5) were obtained in the same manner as Preparation 43.

Preparation 44 5-Octyloxybenzo [b] thiophene-2-carboxylic acid IR (KBr): 1673, 1666, 1600, 1517, 1409, 1267, 1214, 1153, δ 65 cm-1 · NMR (DMSO-d 6, δ) 0.86 (3H, t, J = 6.7Hz), 1.2-1.5 (10H, m), V, 1.7-1.9 (2H, m), 4.02 (2H , t, J = 6.4Hz), 7.13 (1H, dd, J = 8.9 and: 1 0.6Hz), 7.51 (1H, d, J = 0.6Hz), 7.90 (1H, d, J = 9.0Hz), 7.99 (1H, s):? APCI MASS: m / z = 307 (M + +1).

Preparation 45; > 4- [4- (4-Hexyloxyphenyl) piperazin-1-yl] benzoic acid di; hydrochloride IR (KBr): 1668, 1600, 1510, 1228 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.9Hz), 1.2-1.5 (6H, m), 1.6-1.9, '(2H, m), 3.0-3.2 (4H, m), 3.3-3.5 (4H, m), 3.88 (2H, t, J = 6.3Hz), 6.83 (2H, d, J = 9Hz), 6.9-7.1 (4H, m), 7.79 (2H, d, J = 8.8Hz), 12.32, 'h': (1H, s) APCI MASS: m / z = 383 (M + H +)

Preparation 4 6

To a suspension of dimethyl terephthalate (1.94 g) and potassium t-butoxide (2.24 g) in tetrahydrofuran (30 ml) was added 4-pentyloxyacetophenone (1.59 g) in tetrahydrofuran (10 ml) at 70 ° C. The mixture was refluxed for 30 minutes and poured into 1N HCl (50 mL). The mixture was extracted with ethyl acetate (100 mL), and the organic layer was washed with IVO (100 mL), brine (100 mL) and evaporated under reduced pressure. The residue was triturated with acetonitrile (20 mL), collected by filtration and dried under reduced pressure to give 1- (4-methoxycarbonylphenyl) -3- (4-pentyloxyphenyl) propane-1,3-dione (2.41 g) as a yellow solid. .

IR (KBr): 3475, 2956, 2923, 1720, 1606, 1508, 1284, 1176, 1108, 769 cm -1 NMR (CDCl 3, δ): 0.95 (3H, t, J = 7.0Hz), 1 , 3-1.5 (4H, m), 1.7-2.0 (2H, m), 3.96 (3H, s), 4.04 (2H, t, J = 6.5Hz), 6 , 82 (1H, s), 6.96 (2H, d, J = 8.9Hz), 8.0-8.1 (4H, m), 8.14 (2H, m, J = 8.7Hz). , 12-13 (1H, lev) APCI MASS: m / z = 369 (M + H +)

Preparation 47

A solution of 1- (4-methoxycarbonylphenyl) -3- (4-pentyloxyphenyl) propane-1,3-dione (1.00 g) and hydroxylamine hydrochloride (567 mg) in methanol (10 mL) was refluxed: ; 10 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL x 2), brine (50 mL).

The organic layer was dried over magnesium sulfate and the solvents were removed under reduced pressure. The residue was triturated with acetonitrile (10: 1 'ml), collected by filtration and dried under reduced pressure to give methyl 4- [5- (4-pentyloxyphenyl) isoxazol-3-yl] benzoate (0.74 g).

IR (KBr): 2942, 2873, 1716, 1616, 1508, 1280, 1108 cm -1: 1 H NMR (CDCl 3, δ): 0.95 (3H, t, J = 6.9Hz), 1.3 1.6 (4H, m), 1.8-2.0 (2H, m), 3.95 (3H, s), 4.02 (2H, t, J = 6.5Hz), 6.74 ( 1H, s), 6.99 (2H, d, J = 8.8Hz), 7.76 (2H, d, J = 8.8Hz), 7.93 (2H, d, J = 8.5Hz), 8.14 (2H, d, J = 8.5Hz) APCI MASS: m / z = 366 (M + H) +.

Preparation 48

A solution of 4- [4- (8-bromooctyloxy) phenyl] benzoic acid (1 g) in a mixture of sodium methylate (28% solution in methanol) 32 (10 ml) and N, N-dimethylformamide (5 ml) was refluxed for 5 hours. . The reaction mixture was added to a mixture of water and ethyl acetate and the pH was adjusted to 2.0 conc. HCl. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4- [4- (8-methoxyoctyloxy) phenyl] benzoic acid (0.77 g).

IR (KBr): 2935, 1685, 835, 773 cm -1 NMR (CDCl 3, δ): 1.27-1.7 (10H, m), 1.7-1.95 (2H, m), 3 34 (3H, s), 3.38 (2H, t, J = 6.4Hz), 4.01. (2H, t, J = 6.5Hz), 6.99 (2H, d, J = 8.7Hz), 7.58 (2H, d, J = 8.7Hz), 7.66 (2H, d, J = 8.4Hz), 8.15 (2H, d, J = 8.4Hz) APCI MASS: m / z = 339 (M + + H - H 2 O)

Preparation 49

To a suspension of 1-hydroxybenzotriazole (0.283 g) and 6-octyloxymethyl picolinic acid (0.505 g) in dichloromethane (15 ml) was added 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide hydrochloride (WSCD-HCl) (0.473 g). and stirred for 3 hours at ambient temperature. The reaction mixture was poured into water. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 1- (6-octyloxymethyl-picolinoyl) -benzotriazole-3-oxide (737 mg).

IR (neat): 1793, 1654, 1591, 1039 cm -1; 1 '; The following compounds (Preparations 50-66_) were obtained in the same manner as Preparation 49.

'1' Preparation 50 1- [4- (4-Octyloxyphenyl) piperazin-1-yl) benzoyl] benzotriazole-3-oxide: ¹H-IR (KBr): 1783, 1600, 1511, 1232, 1184 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.6Hz), 1.2-1.65 (10H, m), 1.65-1.9 (2H, m), 3 24 (4H, t, J = 5.3Hz), 3.62 (4H, t, J = 5.3Hz), 3.93; (2H, t, J = 6.5Hz), 6.8-7.1 (6H, m), 7.35-7.63 (3H, m), 8.0-8.25 (3H, m) ); Preparation 51 1- [4- [4- [8- (1,2,4-Triazol-1-yl) octyloxy] phenyl] benzoyl] -benzotriazole-3-oxide 33 IR (KBr): 1776, 1600, 1193, 983 cm -1 NMR (CDCl 3, δ): 1.2-2.0 (12H, m), 4.03 (2H, t, J = 6.4Hz), 4.18 (2H, t, J = 7, 1Hz), 7.02 (2H, d, J = 8.7Hz), 7.4-7.63 (3H, m), 7.63 (2H, d, J = 8.7Hz), 7.79 ( 2H, d, J = 8.3Hz), 7.95 (1H, s), 8.06 (1H, s), 8.12 (1H, d, J = 7.7Hz), 8.32 (2H, d, J = 8.3 Hz) APCI MASS: m / z = 511 (M + +1)

Preparation 52 1- [2-Methyl-2- (4-octyloxy-phenoxy) -propionyl] -benzotriazole-3-oxide IR (pure): 2927, 1810, 1504, 1047 cm -1 Preparation 53 1- [2- (4-O-O-oxy-phenoxy) propionyl] benzotriazole-3-oxide IR (KBr): 2954, 1812, 1513, 1232 cm -1

Preparation 54 1 - [(S) -2-tert-Butoxycarbonyl-1,2,3,4-tetrahydro-7-octyloxy-isoquinolin-3-ylcarbonyl] -benzotriazole-3-oxide IR (pure): 2929, 1816, 1739 , 1704, 1392 cm -1> Preparation 55

Succinimido-4- (4-n-octyloxyphenyl) piperazine-1-carboxylate: IR (KBr): 2925, 1758, 1743, 1513, 1241 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.5 (10H, m), 1.65-1.85 "(2H, m), 2.83 (4H, s), 3.0-3.2 (2H, m), 3.6-3.85 (2H, m), 3.91 (2H, V 't, J = 6.5Hz), 6.84 (2H, dd, J = 8.5 and 2.7Hz), 6.90 (2H, dd, J = 8.5 and 2.7Hz) APCI MASS: m / z = 432 (M + +1); · Preparation 56, (; (6-Heptyloxy) -2-naphthyl) methyl succinimidocarbonate IR (KBr): 1878, 1832, 1787, 1735, 1209 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.2Hz), 1.2-1.6 (8H, m), 1.73-2.0: 1 (2H, m), 2.83 (4H, s), 4.07 (2H, t, J = 6.5Hz), 5.44 (2H, s), 7.13 (1H, d, J = 2.4Hz), 7.17 (1H, dd, J = 8.8 and 2.4Hz), 7.44 (1H, dd, J = 8.4 and 1.6Hz), 7.67-7.85 (3H, m)

Preparation 57 34 1- (3,4-Dipentyloxy-benzoyl) -benzotriazole-3-oxide IR (KBr): 2952, 1774, 1594, 1515, 1430, 1272, 1147, 1089 cm -1 NMR (CDCl 3, δ): 0.9 -1.1 (6H, m), 1.3-1.6 (8H, m), 1.8-2.1 (4H, m), 4.0-4.2 (4H, m), 6 , 99 (1H, d, J = 8.5Hz), 7.4-7.6 (3H, m), 7.68 (1H, d, J = 2.0Hz), 7.92 (1H, dd, J = 8.5 and 2.0 Hz), 8.10 (1H, d, J = 8.5 Hz) APCI MASS: m / z = 412 (M + +1).

Preparation 58 1- (7-Octyloxy-coumarin-3-ylcarbonyl) -benzotriazole-3-oxide IR (KBr): 2925, 1754, 1716, 1610, 1548, 1282, 1199, 1172, 1139, 1064, 781, 750 cm @ -1 @ 1 H NMR (DMSO). -dg, δ): 0.86 (3H, t, J = 7.8Hz), 1.2-1.5 (10H, m), 1.6-1.8 (2H, m), 4.11 (2H, t, J = 6.5Hz), 6.9-7.1 (2H, m), 7.41 (1H, t, J = 7.2Hz), 7.54 (1H, t, J = 7.2Hz), 7.72 (1H, d, J = 8.3Hz), 7.82 (1H, d, J = 8.3Hz), 7.99 (1H, d, J = 8.3Hz), 8.72 (1H, s) APCI MASS: m / z = 436 (M + +1)

Preparation 59 1- [4- (4-Pentyloxyphenyl) cinnamoyl] benzotriazole-3-oxide IR (Nujol): 2854, 1778, 1708, 1620, 1597, 1494, 1459, 1434, 1377, 1350, 1250, 1188, 1138, 1086, 978 cm -1. Preparation 60: 1- (5-Octyloxybenzo [b] thiophen-2-ylcarbonyl) -benzotriazole-3 ': 1-oxide IR (KBr): 2950, 1776, 1517, 1342, 1211, 1151 cm -1 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6.7Hz), 1.2-1.5 (10H, m), 1.7-1 , 9 (2H, m), 4.01 (2H, t, J = 6.4Hz), 7.13 (1H, dd, J = 8.8 and 2.4Hz), 7.42 (1H, d, J = 7.1Hz), 7.5-7.6 (3H, m), 7.72 (1H, d, J = 8.4Hz), 7.89 (1H, d, J = 8.8Hz), 7.9-8.1 (2H, m) APCI MASS: m / z = 424 (M + +1) m / z Preparation 61 1- (3-Methyl-5-octyl-benzo [b] furan-2-ylcarbonyl) benzo-triazole-3-oxide IR (KBr): 1776, 1575, 1469, 1363, 1324, 1276, 1114, 1027 cm @ -1 35 NMR (CDCl3, δ): 0.89 (3H, t, J = 6) , 7Hz), 1.2-1.5 (10H, m), 2.6-2.8 (2H, m), 2.71 (3H, s), 2.76 (2H, t, J = 7 , 4Hz), 7.4-7.6 (6H, m), 8.12 (1H, s) APCI MASS: m / z = 406 (M + +1).

Preparation 62 1- (2-Nonylbenzoxazol-5-ylcarbonyl) benzotriazole-3-oxide IR (KBr): 2980, 1783, 1623, 1573, 1276, 1151, 1091, 989 cm -1 NMR (DMSO-d6, δ): 0.84 (3H, t, J = 6.8Hz), 1.1-1.4 (12H, m), 1.81 (2H, t, J = 7.2Hz), 2.96 (3H, t , J = 7.4Hz), 7.41 (1H, t, J = 7.0Hz), 7.54 (1H, t, J = 1.0Hz), 7.74 (2H, t, J = 7, 0Hz), 7.98 (2H, d, J = 7.0Hz), 8.19 (1H, s) APCI MASS: m / z = 407 (M + +1).

Preparation 63 1- [2- (4-Hexyloxyphenyl) benzimidazol-5-ylcarbonyl] -benzotriazole-3-oxide IR (KBr): 3160, 2931, 2863, 1778, 1612, 1502, 1448, 1388, 1294, 1247, 1174 , 1097, 1010, 732 cm -1 NMR (DMSO-d 6, δ): 0.89 (3H, t, J = 6.7Hz), 1.2-1.5 (6H, m), 1.7-1, Δ (2H, m), 4.08 (2H, t, J = 6.4Hz), 7.16 (2H, d, J = 8.7Hz), 7.6-8.4 (9H,; m) , 8.3-8.6 (1H, lev) "1 ;, APCI MASS: m / z = 456 (M + +1): Preparation 64 1- [4- [4- (8-Methoxy-octyloxy) ) phenyl] benzoyl] benzotriazole-3-oxide [nu] IR (KBr): 2931, 1793, 1770, 1600 cm <-1>. NMR (CDCl3, [delta]): 1.2-1.7 (10H, m), 1.7 -1.93 (2H, m), 3.34 (3H, s), 1 '3.38 (2H, t, J = 6.4Hz), 4.03 (2H, t, J = 6.5Hz) ), 7.03 (2H, d, J = 8.8Hz), 7.4-7.7 (3H, m), 7.63 (2H, d, J = 8.8Hz), 7.79 (2H) , d, J = 8.6Hz), 8.12 (1H, d, J = 8.2Hz), 8.32 (2H, d, J = 8.6Hz) i; Preparation 65 1- [4- [ 4- (4-Hexyloxyphenyl) piperazin-1-yl] benzoyl] -: benzotriazole-3-oxide IR (KBr): 1770, 1604, 1510, 1232, 1186 cm -1 NMR (CDCl 3, δ): 0.91 ( 3H, t, J = 6.6Hz), 1.2-1.6 (6H, m), 1.6-1.9 (2H , 36m), 3.1-3.3 (4H, m), 3.5-3.7 (4H, m), 3.93 (2H, t, J = 6.5Hz), 6.87 ( 2H, d, J = 9.2Hz), 6.96 (2H, d, J = 9.2Hz), 7.00 (2H, d, J = 9.0Hz), 7.3-7.7 (3H , m), 8.10 (1H, d, J = 8.2Hz), 8.15 (2H, d, J = 9.0Hz) APCI MASS: m / z = 500 (M + H +)

Preparation 66 1- [4- [5- (4-Pentyloxy-phenyl) -isoxazol-3-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 2950, 2837, 1774, 1616, 1508, 1452, 1251, 1006 cm 1 H NMR (CDCl 3, δ): 0.95 (3H, t, J = 7.1 Hz), 1.3-1.5 (4H, m), 1.8-2.0 (2H, m), 4.04 (2H, t, J = 6.5Hz), 6.81 (1H, s), 7.0-7.1 (3H, m), 7.4-7.6 (3H, m), 7.80 (2H, d, J = 8.8Hz), 8.0-8.2 (3H, m), 8.40 (2H, d, J = 8.4Hz) APCI MASS: m / z = 469 (M + H) +

Preparation 67

To a suspension of 1-hydroxybenzotriazole (0.20 g) and 4- (4-pentylphenyl) cinnamic acid (0.40 g) in dichloromethane (12.0 mL) was added 1-ethyl-3- (31-dimethylaminopropyl) carbodiimide hydrochloride (0.33 g) (WSCD-HCl) and the mixture was stirred for 12 hours at ambient temperature. The reaction mixture was diluted with dichloromethane, and washed with brine and dried over magnesium sulfate. The magnesium sulfate was separated by filtration: then the filtrate was evaporated and triturated with acetonitrile to give 1- [4- (4-pentylphenyl) -cinnamoyl] benzotriazole-3-oxide (0.24 g).

NMR (CDCl 3, δ): 0.91 (3H, t, J = 6, 6Hz), 1.20-1.50 (4H, m), 1.50-1.75 (2H, m), 2.66 (2H, t, J = 8.0Hz), 7.20-8.25 (1H, m), 8.55 (1H, d, J = 8.4Hz) APCI MASS: m / z = 41-2 (M ++ 1) '1 The following compounds (Preparations 68-73) were obtained in the same manner as Preparation 67.

Preparation 68 1- [3- [4- (4-Pentyloxy-phenyl) -phenyl] -2-propanoyl] -benzotriethyl-sol-3-oxide NMR (CDCl 3, δ): 0.90-1.05 (3H, m) , 1.30-1.65 (4H, m), 1.70-1.95 (2H, m), 3.10-3.60 (4H, m), 3.90-4.10 (2H, m), 6.88-7.08 (2H, m), 7.20-37 8.50 (10H, m) APCI MASS: m / z = 430 (M + +1).

Preparation 69 1- [4- (4-Heptylphenyl) cinnamoyl] benzotriazole-3-oxide NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.7Hz), 1.20-1.50 (8H) , m), 1.50-1.80 (2H, m), 2.66 (2H, t, J = 7.6Hz), 6.70-8.60 (12H, m) APCI MASS: m / z = 440 (M ++ 1)

Preparation 70 1- [3- [4- (4-Pentylphenyl) phenyl] -2-propanoyl] benzotriazole-3-oxide NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.8Hz), 1 , 20-1.50 (4H, m), 1.50-1.76 (2H, m), 2.63 (2H, t, J = 7.4Hz), 3.21 (2H, t, J = 7.3Hz), 3.51 (2H, t, J = 7.3Hz), 7.20-7, 45 (4H, m), 7.45-7.70 (5H, m), 7.78 ( 1H, dt, J = 1.0 and 7.2Hz), 8.00 (1H, d, J = 8.2Hz), 8.42 (1H, d, J = 8.4Hz) APCI MASS: m / z = 414 (M ++ 1)

Preparation 71 1- [3- (6-Heptyloxy-naphthalen-2-yl) -propanoyl] -benzotriazole-3-oxide: NMR (CDCl 3, δ): 0.80-1.10 (3H, m), 1.20-1. 70 (8H, m), 1.70-2.00 (2H, m), 3.10-3.70 (4H, m), 4.00-4.18 (2H, m), 6.80- 8.50 (10H, m) APCI MASS: m / z = 432 (M + + 1)

Preparation 72 / :: 1- [3- (6-Heptyloxynaphthalen-2-yl) -propenoyl] -benzotriazole-3-oxide NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1, 20-1.65 (8H, m), 1.75-1.95 (2H, m), 4.10 (2H, d, J = 6.5Hz), 6.75-8.62 ( 8H, m) "; 1" APCI MASS: m / z = 430 (M + +1)

Preparation 73; · 1- (4-Hexyl-phenyl-benzoyl) -benzotriazole-3-oxide NMR (CDCl3, δ): 0.90 (3H, t, J = 4.4Hz), 1.2-1.5 (6H, m), 6-1.8 (2H, m), 2.68 (2H, t, J = 8.0Hz), 7.32 (2H, d, J = 8.2Hz), 7.4-7.7 (5H , m), 7.81 (2H, d, J = 6.6Hz), 8.10 (2H, d, J = 8.1Hz), 8.32 (2H, d, J = 7.6Hz) APCI- MASS: m / z = 400 (M ++ 1)

Preparation 74 38

To a solution of 4-octyloxyphenol (1 g) in dimethylformamide (10 ml) and pyridine (0.364 ml) was added N, N'-disuccinimidyl carbonate (1.16 g). The mixture was stirred for 12 hours at ambient temperature. The reaction mixture was added to a mixture of water and ethyl acetate. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure to give 4-octyloxyphenylsuccinimidyl carbonate (0.59 g).

IR (KBr): 2927, 1876, 1832, 1735 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.3Hz), 1.2-1.55 (10H, m), 1.67-1.87 (2H, m), 2.87 (4H, s), 3.94 (2H, t, J = 6.5Hz), 6.89 (2H, d, J = 9.2Hz) ), 7.17 (2H, d, J = 9.2Hz) APCI MASS: m / z = 364 (M + +1).

The following compounds (Preparations 75-8g) were obtained in the same manner as Preparation 1.

Preparation 75

Methyl 4- [4- (6-phenylpyridazin-3-yloxy) phenyl] benzoate IR (KBr): 1708, 1427, 1280, 1187, 1112 cm -1 NMR (CDCl 3, δ): 3.95 (3H, s) ), 7.2-7.7 (10H, m), 7.92 (1H, d, '' J = 9.2Hz), 8.0-8.2 (4H, m) V: APCI- MASS: m / z = 383 (M + H) +; Preparation 7 6 "Methyl 4- [4- (5-bromopentyloxy) phenyl] benzoate V; IR (KBr): 2946, 2871, 1716, 1602, 1294, 1199, 1112, 837 cm -1 NMR (CDCl 3, δ): 1 , 7-2.0 (6H, m), 3.45 (2H, t, J = 6.7Hz), 3.93 (3H, i ', s), 4.02 (2H, t, J = 6 , 1Hz), 6.97 (2H, d, J = 8.7Hz), 7.56 (2H, d, J = 8.7Hz), 7.61 (2H, d, J = 8.3Hz) , 8.07 (2H, d, J = 8.3Hz) APCI MASS: m / z = 378 (M + H) + C 11;

Methyl 4- [4- (5-phenoxypentyloxy) phenyl] benzoate 1 IR (KBr): 2944, 2931, 1720, 1600, 1492, 1197, 1110 cm -1 NMR (CDCl 3, δ): 1.6-1, Δ (2H, m), 1.8-2.0 (4H, m), 3.93 (3H, s), 4.00 (2H, t, J = 6.3Hz), 4.04 (2H, t, J = 6.3Hz), 6.9-7.1 (5H, m), 7.3-7.4 39 (2H, m), 7.56 (2H, d, J = 8.7Hz) , 7.62 (2H, d, J = 8.3Hz), 8.07 (2H, d, J = 8.3Hz) APCI MASS: m / z = 391 (M + H) +.

Preparation 78 1- [2- (4-Cyclohexyl-phenylamino) -ethyl] -2-oxazolidone hydrochloride IR (KBr): 2923.6, 2852.2, 1747.2, 1683.6 cm -1 NMR (DMSO-d6, δ ): 1.1-1.5 (6H, m), 1.6-1.9 (4H, m), 2.3-2.6 (1H, m), 3.3-3.5 (4H) , m), 3.58 (2H, dd, J = 9.4 and 7.4Hz), 4.22 (2H, dd, J = 9.4 and 7.4Hz), 7.1-7.4 ( 4H, m)

Preparation 79

Methyl 4- [4- (8-hydroxyoctyloxy) phenyl] benzoate IR (KBr): 3250, 2933, 2856, 1724, 1602, 1436, 1292, 1199 cm -1 NMR (CDCl 3, δ): 1.3-1 , 9 (12H, m), 3.6-3.8 (2H, lev), 3.93 (3H, s), 4.00 (2H, t, J = 6.7Hz), 4.82 (1H , s), 7.68 (2H, d, J = 8.7Hz), 7.56 (2H, d, J = 8.7Hz), 7.62 (2H, d, J = 8.3Hz), δ , 07 (2H, d, J = 8.3Hz) APCI MASS: m / z = 357 (M + H +)

Preparation 80 L, Methyl 4- [4- (6-bromohexyloxy) phenyl] benzoate V 1 IR (KBr): 2937, 2861, 1724, 1602, 1529, 1436, 1292, 1199, 1112 cm -1; NMR (CDCl 3, δ): 1.5-2.0 (8H, m), 3.43 (2H, t, J = 6.8Hz), 3.93 (3H, s), 4.02 (2H, t, J = 6.3Hz), 6.98 (2H, d, J = 8.8Hz), 7.56 (2H, d, J = 8.8Hz), 7.62 (2H, d, J = 8 , 4Hz), 8.07 (2H, d, J = 8.4Hz) APCI MASS: m / z = 391 (M + H +); Preparation 81, 4- [4- (5-Bromopentyloxy) phenyl IR (KBr): 2942, 2867, 1604, 1515, 1477, 1286 cm -1: NMR (CDCl 3, δ): 1.5-2.0 (6H, m), 3.44 (2H, t, J = 6.7Hz); 3.99 (2H, t, J = 6.2Hz), 6.95 (2H, d, J = 8.7Hz), 7.3-7.6 (6H, m ) APCI MASS: m / z = 399 (M + H +)

Preparation 82 40 8- [4- (4-Methoxycarbonylphenyl) phenoxy] octanoylpiperidine IR (KBr): 2935, 2852, 1720, 1639, 1604, 1438, 1292 cm -1 NMR (CDCl 3, δ): 1.3-1, 9 (16H, m), 2.34 (2H, d, J = 7.6Hz), 3.4-3.6 (4H, m), 3.93 (3H, s), 3.99 (2H, t, J = 6.4Hz), 6.97 (2H, d, J = 8.8Hz), 7.55 (2H, d, J = 8.8Hz), 7.61 (2H, d, J = 8 , 6Hz), 8.07 (2H, d, J = 8.6Hz) APCI MASS: m / z = 438 (M + H +)

Preparation 83

Methyl 6- [4- (4-n-heptyloxyphenyl) piperazin-1-yl] nicotinate IR (KBr): 2933, 2859, 1726, 1608, 1513, 1430, 1280, 1245 cm -1 1 H NMR (CDCl 3, δ) 0.89 (3H, t, J = 6.7Hz), 1.2-1.8 (10H, m), 3.17 (4H, t, J = 4.9Hz), 3.8-4, 0 (9H, m), 6.65 (1H, d, J = 9.1Hz), 6.86 (2H, d, J = 9.1Hz), 6.96 (2H, d, J = 9.1Hz) ), 8.05 (1H, dd, J = 9.1 and 2.3Hz), 8.82 (1H, d, J = 2.3Hz) APCI MASS: m / z = 412 (M + H +)

Preparation 84

Methyl 6- [4- [4- (8-bromooctyloxy) phenyl] piperazin-1-yl] -nicotinate IR (KBr): 2933, 2861, 1724, 1608, 1513, 1430, 1280 cm -1 NMR (CDCl δ): 1.2-2.0 (12H, m), 3.17 (4H, t, J = 5.0Hz), 3.40 (2H, t, J = 6.8Hz), 3.8- 4.0 (9H, m), 6.64 (1H, d, J = 9.0Hz), 6.85 (2H, d, J = 9, 1Hz), 6.96 (2H, d, J = 9 , 1Hz), 8.05 (1H, dd, J = 9.0 and 2.2Hz), 8.82 '(1H, d, J = 2.2Hz) APCI MASS: m / z = 504 (M + H +):: Preparation 85 4- [4- (7-Bromo-heptyloxy) -phenyl] -bromobenzene IR (KBr): 2935, 1, 2856, 1, 1604.5 cm -1, NMR (CDCl 3, δ): 1.18 -1.65 (6H, m), 1.70-2.02 (4H, m), 3.41 (2H, t, J = 6, 8Hz), 3.99 (2H, t, J = 6, 4Hz), 6.95 (2H, d, J = 8.6Hz), 7.40 (2H, d, J = 8.6Hz), 7.46 (2H, d, J = 8.6Hz), 7, 52 (2H, d, J = 8.6Hz); · Preparation 8 6 4- [4- (8-Bromooctyloxy) phenyl] bromobenzene NMR (CDCl 3, δ): 1.22-1.65 (8H, m), 1.65-1.95 (4H, m), 3, 41 (2H, t, J = 6.8Hz), 3.99 (2H, t, J = 6.4Hz), 6.95 (2H, d, J = 8.6Hz), 7.40 (2H, d) , 41 J = 8.6Hz), 7.46 (2H, d, J = 8.6Hz), 7.52 (2H, d, J = 8.6Hz)

Preparation 87

Methyl (E) -3- [4- [4- (5-hexenyloxy) phenyl] phenyl] acrylate NMR (CDCl 3, δ): 1.50-1.72 (2H, m), 1.72-1.95 (2H, m), 2.05-2.14 (2H, m), 3.82 (3H, s), 4.01 (2H, t, J = 6.3Hz), 4.95-5.10 (2H, m), 5.70-5.93 (1H, m), 6.46 (1H, d, J = 16Hz), 6.97 (2H, d, J = 8.7Hz), 7.54 (2H, d, J = 8.7Hz), 7.58 (4H, s), 7.72 (1H, d, J = 16Hz) APCI MASS: m / z = 337 (M + +1).

Preparation 88 4-Bromo-4 '- (4-methylpentyloxy) biphenyl IR (KBr): 2956.3, 2871.5, 1606.4 cm -1 NMR (CDCl 3, δ): 0.93 (6H, d, J = 6.6Hz), 1.25-1.45 (2H, m), 1.62 (1H, sept, J = 6.6Hz), 1.72-1.93 (2H, m), 3.98 (2H, t, J = 6.6Hz), 6.95 (2H, d, J = 8.6Hz), 7.30-7.60 (6H, m) APCI MASS: m / z = 332, 334 (M +, M ++ 2)

The following compounds (Preparations 89 - 9J0) were obtained in the same manner as Preparation 2.

Preparation 89: ι 'N- [4- [2- (4-Methylpentyl) -2,3-dihydro-4H-1,2,4-triazol-3-one-4-d d. yl] phenyl] piperazine trifluoroacetate IR (KBr): 1668.1, 1519.6, 1203.4, 1176.4, 1130.1 cm -1 NMR (DMSO-d 6, δ): 0.86 (6H, d, J = 6.6Hz), 1.1-1.3 (2H, m), 1.4-1.8 (3H, m), 3.1-3.3 (4H, m), 3.3- 3.5 (4H, m), 3.70 (2H, t, J = 7.0Hz), d: 7.11 (2H, d, J = 9.0Hz), 7.53 (2H, d, J = 9.0Hz), 8.35 (1H, s), 8.90 (2H, s)

Preparation 90: d 1- (4-Phenylcyclohexyl) piperazine trifluoroacetate IR (KBr): 1677.8, 1177.6, 1133, 9 cm -1 NMR (DMSO-d 6, δ): 1.4-1.8 ( 4H, m), 1.8-2.25 (4H, m), 2.4-2.7 (1H, dm), 3.2-3.7 (9H, m), 4.54 (2H, lev s), 7.0-7.4 (5 H, m), 9.32 (1H, 1.1, lev s) ÄPCI MASS: m / z = 245 (M + + H) 42

The following compounds (Preparations 91-103) were obtained in the same manner as Preparation 3.

Preparation 91

Methyl 6- [4- (4-octyloxyphenyl) piperazin-1-yl] nicotinate IR (KBr): 2923, 1726, 1608, 1515, 1278, 1116 cm -1 @ 1 H NMR (CDCl3, .delta.): 0.88 (3H, t , J = 6.8Hz), 1.2-1.5 (10H, m), 1.7-1.8 (2H, m), 3.1-3.2 (4H, m), 3.8 -4.0 (9H, m), 6.64 (1H, d, J = 9.0Hz), 6.8-7.0 (4H, m), 8.04 (1H, dd, J = 9, 0 and 2.4Hz), 8.81 (1H, d, J = 2.4Hz) APCI MASS: m / z = 426 (M + H +)

Preparation 92 4- [4- [4- [2- (4-Methylpentyl) -2,3-dihydro-4H-1,2,4-triazol-3-one-4-yl] phenyl] piperazin-1-yl ] benzonitrile IR (KBr): 2217.7, 1685.5 cm -1 NMR (CDCl 3, δ): 0.90 (6H, d, J = 6.6Hz), 1.2-1.4 (2H, m ), 1.5-2.0 (3H, m), 3.3-3.4 (4H, m), 3.4-3.6 (4H, m), 3.83 (2H, t, J). = 7.4Hz), 6.92 (2H, d, J = 9.0Hz), 7.01 (2H, d, J = 9.0Hz), 7.43 (2H, d, J = 9.0Hz) , 7.54 - (2H, d, J = 9.0Hz), 7.62 (1H, s)

Preparation 93: '3-Fluoro-4- [4- (4-methoxyphenyl) piperazin-1-yl] benzonitrile:' IR (KBr): 2225.5, 1510.0, 1240.0 cm -1 NMR (CDCl , δ): 3.1-3.55 (8H, m), 3.79 (3H, s), 6.7-7.1 (6H, m), 7.3-7.5 (1H, m) ) • 'Preparation 94:? 3-Chloro-4- [4- (4-n-hexyloxyphenyl) piperazin-1-yl] -' benzonitrile IR (KBr): 2223.5, 1592.9, 1510.0, 1490.7, 1236.1 cm -1: 1 H NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.7Hz), 1.3-1.6 (6H , m), 1.7-1.9 (2H, m), 3.2-3.4 (8H, m), 3.92 (2H, t, J = 6.6Hz), 6.85 (2H , d, J = 9.3Hz), 6.94 (2H, d, J = 9.3Hz), 7.08 (1H, d, J = 8.4Hz), 7.53 (1H, dd, J = 8.4 and ···: 1.9Hz), 7.64 (1H, d, J = 1.9Hz) APCI MASS: m / z = 398 (M + + H)

Preparation 95 43

Ethyl 3- [4- (4-n-hexyloxyphenyl) piperazin-1-yl] -6-pyridazine carboxylate IR (KBr): 1729.8, 1587.1, 1511.9, 1245.8 cm -1 NMR (CDCl , δ): 0.90 (3H, t, J = 6.5Hz), 1.2-1.4 (6H, m), 1.44 (3H, t, J = 7.1Hz), 1.65 -1.85 (2H, m), 3.1-3.25 (4H, m), 3.8-4.0 (6H, m), 4.46 (2H, q, J = 7.1Hz) , 6.8-7.0 (5H, m), 7.91 (1H, d, J = 9.6Hz) APCI MASS: m / z = 413 (M + + H).

Preparation 96 4- (4-Piperidinopiperidin-1-yl) benzonitrile IR (KBr): 2217.7, 1602.6, 1511.9 cm -1 1 H NMR (CDCl 3, δ): 1.35-1.75 (8H, m), 1.92 (2H, d, J = 12.9Hz), 2.3-2.6 (5H, m), 2.86 (2H, td, J = 12.8 and 2.6Hz), 3.90 (2H, d, J = 12.8Hz), 6.84 (2H, d, J = 9.1Hz), 7.46 (2H, d, J = 9.1Hz) APCI MASS: m / z = 270 (M ++ H)

Preparation 97 5- [4- (4-n-Hexyloxyphenyl) piperazin-1-yl] picolinonitrile IR (KBr): 2223.5, 1575.6, 1511.9, 1241.9 cm -1 1 H NMR (CDCl 3, δ) 0.90 (3H, t, J = 6.5Hz), 1.2-1.55 (6H, m), 1.7-1.85 (2H, m), 3.22 (4H, t, J = 5.1Hz, 3.52 (4H, t, J = 5.1Hz), 3.92 (2H, t, J = 6.5Hz), 6.86 (2H, d, J = 9.4Hz) ), 6.93 (2H, d, J = 9.4Hz), 7.13 (1H, dd, J = 8.8 and 3.0Hz), 7.53 (1H, d, J = 8.8Hz) , 8.35 (1H, d, J = 3.0Hz) APCI MASS: m / z = 365 (M + + H)::: Preparation 98 4- [4- (4-Cyclohexylphenyl) -piperazin-1-yl ] benzonitrile: 1 H IR (KBr): 2219, 7, 1606.4, 1513.8, 1238.1 cm -1 NMR (CDCl 3, δ): 1.1-1.5 (6H, m), 1 65-2.0 (4H, m), 2.44 (1H, m), 3.30 (4H, t, J = 5.1Hz), 3.46 (4H, t, J = 5.1Hz), 6.90 (4H, d, J = 8.9Hz), 7.14 (2H, d, J = 8.9Hz), 7.52 (2H, d, J = 8.9Hz) APCI MASS: m / z = 346 (M + + H): 1; Preparation 99 4- [4- (4-n-Hexylphenyl) piperazin-1-yl] benzonitrile IR (KBr): 2925.5, 2850.3, 2213.9, 1604.5, 1513.8, 1234.2, 44 944.9 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.4Hz), 1.2-1.45 (6H, m), 1.45-1.7 (2H, m), 2.54 (2H, t, J = 7.6Hz), 3.2-3.4 (4H, m), 3.4-3.6 (4H, m), 6.89 (2H, d, J = 8.5Hz), 6.91 (2H, d, J = 8.9Hz), 7.11 (2H, d, J = 8.5Hz), 7.52 (2H, d, J = 8 , 9 Hz)

Preparation 100 1- [2- (4-n-Hexyl-phenylamino) -ethyl] -2-oxazolidone hydrochloride IR (KBr): 2925, 5, 2852.2, 1753, 0, 1729, 8, 1267.0 cm -1 NMR (DMSO-dg) , δ): 0.85 (3H, t, J = 6.5Hz), 1.1-1.4 (6H, m), 1.45-1.7 (2H, m), 2.56 (2H , t, J = 7.6Hz), 3.3-3.53 (4H, m), 3.57 (2H, t, J = 7.9Hz), 4.24 (2H, t, J = 7, 9Hz), 7.24 (4H, s) APCI MASS: m / z = 291 (M + + H)

Preparation 101 4- [4- (4-Phenyl-cyclohexyl) -piperazin-1-yl] -benzonitrile IR (KBr): 2212.0, 1602.6, 1513.8, 1249.6 cm -1 NMR (CDCl 3, δ): 1 , 3-1.8 (4H, m), 1.9-2.2 (4H, m), 2.3-2.6 (2H, m), 2.75 (4H, t, J = 5, 0Hz), 3.34 (4H, t, J = 5.0Hz), 6.86 (2H, d, J = 8.9Hz), 7.1-7.4 (5H, m), 7.49 ( 2H, d, J = 8.9Hz) APCI MASS: m / z = 346 (M + + H): 1 (· (Preparation 102

Methyl 6- [4- (4-hydroxyphenyl) piperazin-1-yl] nicotinate: IR (KBr): 3411, 1691, 1602, 1510, 1432, 1249, 1147 cm -1 NMR (DMSO-d 6, δ): 3.0-3.1 (4H, m), 3.7-3.9 (7H, m), 6.67 (2H, d, J = 8.8Hz), 6.84 (2H, d, J) = 8.8Hz), 6.93 (1H, d, J = 9.1Hz), 7.97 (1H, V, dd, J = 2.4 and 9.1Hz), 8.66 (1H, d, J = 2.4Hz), 8.88 (1H, s) APCI MASS: m / z = 314 (M + H) +; Preparation 103 IN-Decylindole-5-carboxylic acid IR (KBr): 2921, 2854, 1679, 1612, 1427, 1313, 1199 cm -1 NMR (DMSO-d 6, δ): 0.84 (3H, t, J = 6.8Hz), 1.1-1.3 (14H, m), 1.6-1.8 (2H, m), 4.19 (2H, t, J = 6.9Hz), 6.57 (1H, s), 7.4-7.8 (3H, m), 8.23 (1H, s), 12.40 (1H, s) 45 APCI-MASS: m / z = 302 (M + H +). )

The following compounds (Preparations 104-111) were obtained in the same manner as Preparation 10.

Preparation 104 (E) -Methyl 4- (4-n-butoxyphenyl) cinnamate IR (KBr): 2958, 2939, 2873, 1720, 1637, 1498, 1313, 1195, 1170 cm -1 NMR (CDCl 3, δ): δ , 98 (3H, t, J = 7.3Hz), 1.4-1.8 (4H, m), 3.81 (3H, s), 4.00 (2H, t, J = 6.4Hz) , 6.45 (1H, d, J = 16.0Hz), 6.97 (2H, d, J = 8.7Hz), 7.5-7.7 (6H, m), 7.72 (1H, d, J = 16.0Hz) APCI MASS: m / z = 311 (M + H +)

Preparation 105

Methyl (E) -3- [4- [4- (4-methylpentyloxy) phenyl] phenyl] acrylate IR (KBr): 2956.3, 2873.4, 1720.2, 1635.3, 1600.6 cm 1 H NMR (CDCl 3, δ): 0.93 (6H, d, J = 6.5Hz), 1.28-1.50 (2H, m), 1.50-1.95 (3H, m) ), 3.82 (3H, s), 3.99 (2H, t, J = 6.6Hz), 6.44 (1H, d, J = 16.0Hz), 6.97 (2H, d, J). = 8.7Hz), 7.49-7.65 (6H, m), 7.71 (1H, d, J = 16Hz): APCI MASS: m / z = 339 (M + +1). I ', Preparation 106' Methyl (E) -3- [4- [4- (6-fluorohexyloxy) phenyl] phenyl] -acrylate NMR (CDCl 3, δ): 1.23-2.00 (8H, m) , 3.81 (3H, s), 4.01 (2H, t, J = 6.4Hz), 4.47 (2H, dt, J = 47.4 and 6.0Hz), 6.45 (1H, d, J = 16.0Hz), δ 6.96 (2H, d, J = 8.8Hz), 7.45-7.63 (6H, m), 7.72 (1H, d, J = 16 , 0Hz) '' C APCI MASS: m / z = 357 (M + +1)

Preparation 107 µl Methyl (E) -3- [4- [4- (6-methoxyhexyloxy) phenyl] phenyl] acrylate APCI MASS: m / z = 369 (M +)

Preparation 108 46

Methyl (E) -3- [4- [4- (8-methoxy-octyloxy) -phenyl] -phenyl] -acrylate IR (KBr): 2935.1 / 2858.0, 1722.1, 1637.3, 1602.6 cm 1 NMR (CDCl 3, δ): 1.30-1.70 (10H, m), 1.70-1.92 (2H, m), 3.33 (3H, s), 3.37 (2H , t, J = 6, 5H.z), 3.81 (3H, s), 4.00 (2H, t, J = 6.5Hz), 6.45 (1H, d, J = 16.0Hz) , 6.97 (2H, d, J = 8.8Hz), 7.46-7.78 (6H, m), 7.72 (1H, d, J = 16.0Hz) APCI MASS: m / z = 397 (M ++ 1)

Preparation 109

Methyl (E) -3- [4- (4-hydroxyphenyl) phenyl] acrylate IR (KBr): 3409.5, 1695.1 cm -1 NMR (DMSO-d 6, δ): 3.73 (3H) , s), 6.64 (1H, d, J = 16Hz), 6.85 (2H, d, J = 8.6Hz), 7.50-7.83 (5H, m) APCI MASS: m / z = 255 (M ++ 1)

Preparation 110

Methyl (E) -3- [4- [4- (7-methoxy-heptyloxy) -phenyl] -phenyl] -acrylate NMR (CDCl 3, δ): 1.32-1.70 (8H, m), 1.70-1 , 92 (2H, m), 3.34 (3H, s),. 3.38 (2H, t, J = 6.4Hz), 3.81 (3H, s), 4.00 (2H, t, J = 6.5Hz), 6.45 '· (1 H, d, J = 16.0Hz), 6.97 (2H, d, J = 8.8Hz), 7.47-7, 65 (6H, m), 7.70 (1H, d, J = 16Hz) 1 APCI- MASS: m / z = 383 (M + +1)

Preparation 111; '' Methyl (E) -3- [4- [4- (7-fluoro-heptyloxy) -phenyl] -phenyl] - ""; acrylate IR (KBr): 2937.1, 2861.8, 1722.1, 1637, 3, 1600.6 cm-1 The following compound was obtained in the same manner as Preparation 20.

1'1 (Preparation 112

Methyl 3- [4- (4-heptylphenyl) phenyl] propanoate NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.5Hz), 1.15-1.50 (8H, m), 1.50-1.77 47 (2H, m), 2.52-2.73 (4H, m), 2.99 (2H, t, J = 7.8Hz), 3.68 (3H, s) , 7.18-7.35 (4H, m), 7.40-7.58 (4H, m) APCI MASS: m / z = 339 (M + +1).

The following compounds (Preparations 113-164) were obtained in the same manner as Preparation 32.

Preparation 113 4- (4-Octylphenyl) -2,4-dihydro-3H-1,2,4-triazol-3-one-2-ylacetic acid IR (KBr): 2923.6, 1704.8, 1224.6 cm 1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.7Hz), 1.1-1.4 (10H, m), 1.4-1.7 (2H, m) ), 2.60 (2H, t, J = 7.2Hz), 4.38 (2H, s), 7.32 (2H, d, J = 8.5Hz), 7.58 (2H, d, J) = 8.5 H z), 8.43 (1H, s)

Preparation 114 1-Heptyl-4- (4-carboxyphenyl) pyrazole IR (KBr): 3106, 2917, 1687, 1612, 1425, 1295, 1184, 952, 860, 773 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.8Hz), 1.1-1.4 (8H, m), 1.7-1.9 (2H, m), 4.11 (2H, t, J = 7.0Hz), 7.69 (2H, d, J = 8.5Hz), 7.91 (2H, d, J = 8.5Hz), 7.98 (1H, s), 8.32 (1H) , s), 12.82 (1H, lev) APCI MASS: m / z = 287 (M + H +):. Preparation 115; 1,6- [4- (4-Octyloxyphenyl) piperazin-1-yl] nicotinic acid IR (KBr pellet): 2919, 2854, 1697, 1608, 1515, 1429, 1263, 1245, 122 cm-1 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6.7Hz), 1.1-1.5 (10H, m), 1.6-1.8: (2H , m), 3.0-3.2 (4H, m), 3.7-3.9 (4H, m), 3.88 (2H, t, J = 6.4Hz),: 6.7- 7.0 (5H, m), 7.95 (1H, dd, J = 9.0 and 1.1Hz), 8.64 (1H, d, J = 1.1Hz) APCI MASS: m / z = 412 (M + H +)

Preparation 116. : 2- (4-Hexyloxyphenyl) -benzoxazole-5-carboxylic acid IR (KBr): 2952, 1689, 1677, 1619, 1500, 1415, 1299, 1172, 1024 cm-1 48 NMR (DMSO-d 6, δ): 0, 89 (3H, t, J = 6.7Hz), 1.2-1.5 (6H, m), 1.7-1.9 (2H, m), 4.09 (2H, t, J = 6) , 5Hz), 7.16 (2H, d, J = 8.8Hz), 7.84 (1H, d, J = 8.5Hz), 8.01 (1H, dd, J = 8.5 and 1, 5Hz), 8.15 (2H, d, J = 8.8Hz), 8.26 (1H, d, J = 1.5Hz) APCI MASS: m / z = 340 (M + H +)

Preparation 117 4- [4- (4-n-Butyloxyphenyl) phenyl] benzoic acid IR (KBr): 2958, 2873, 1689, 1600, 1537, 1396 cm

Preparation 118 6- (4-Heptyloxyphenyl) nicotinic acid IR (KBr): 2858, 1699, 1674, 1589, 1425, 1180, 1016, 781 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz), 1.2-1.5 (8H, m), 1.6-1.8 (2H, m), 4.04 (2H, t, J = 6.4Hz), 7, 06 (2H, d, J = 8.9Hz), 8.03 (1H, d, J = 8.2Hz), 8.13 (2H, d, J = 8.9Hz), 8.27 (1H, dd) , J = 8.2 and 2.2Hz), 9.09 (1H, d, J = 2.2Hz), 13.31 (1H, lev) APCI MASS: m / z = 314 (M + H +)

Preparation 119 ', 5- (4-Octyloxyphenyl) isoxazole-3-carboxylic acid V: IR (KBr pellet): 2923, 2852, 1704, 1612, 1440, 1272 ,; 1-1178 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.8Hz), 1.2-1.6 (10H, m), 1.6-1 Δ: 9 (2H, m), 4.03 (2H, t, J = 6.5Hz), 7.08 (2H, d, J = 8.9Hz), 7.25 (1H, s), . : 1. 7.86 (2H, d, J = 8.9Hz) APCI MASS: m / z = 318 (M + H +) 1 'Preparation 120 2- (2-Octyloxypyridin-5-yl) benzoxazole-5 Carboxylic acid IR (KBr): 2954, 2923, 2854, 1697, 1683, 1625, 1488, 1290 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 7.6Hz), 1 , 2-1.5 (10H, m), 1.7-1.8 / (2H, m), 4.36 (2H, t, J = 6.6Hz), 7.04 (1H, d, J = 8.7Hz), 7.88 (1H, d, J; 8.5Hz), 8.04 (1H, dd, J = 8.5 and 1.6Hz), 8.29 (1H, d, J = 1.6Hz, 8.43 (1H, dd, J = 8.7 and 2.4Hz), 8.99 (1H, d, J = 2.4Hz), 13.0-13.2 (1H, lev) APCI MASS: m / z = 369 (M + H +)

Preparation 121 49 2- [4- (4-Hexyl-phenyl) -phenyl] -benzoxazole-5-carboxylic acid IR (KBr): 2923, 2854, 1683, 1411, 1299, 1054 cm @ -1 APCI: m / z = 400 (M +). + H +)

Preparation 122 6- [4- (4-n-Butyloxyphenyl) phenyl] nicotinic acid IR (KBr): 3406, 2958, 1691, 1591, 1394, 1284, 1253 cm-1 NMR (DMSO-d6, δ): 0.94 (3H, t, J = 7.3Hz), 1.4-1.8 (4H, m), 4.01 (2H, t, J = 6.4Hz), 7.02 (2H, d, J = 8.7Hz), 7.57 (2H, d, J = 8.7Hz), 7.61 (2H, d, J = 8.2Hz), 7.83 (2H, d, J = 8.2Hz), 8.05 (1H, d, J = 8.5Hz), 8.22 (1H, dd, J = 8.5 and 1.6Hz), 9.14 (1H, d, J = 1.6Hz) APCI- MASS: m / z = 348 (M + H +)

Preparation 123 4- [4- (5-Phenoxypentyloxy) phenyl] benzoic acid NMR (DMSO-d6, δ): 1.5-1.7 (2H, m), 1.7-1.9 (4H, m), 3.98 (2H, t, J = 6.3Hz), 4.05 (2H, t, J = 6.1Hz), 6.8-7.0 (3H, m), 7.05 (2H, d) , J = 8.6Hz), 7.25 (2H, t, J = 8.2Hz), 7.68 (2H, d, J = 8.5Hz), 7.75 (2H, d, J = 8, 2Hz), 7.98 (2H, d, J = 8.2Hz), 12.8-13.0 (1H, levs) APCI MASS: m / z = 375 (MH +) ('(Preparation 124': 1 '; 4- [5- (4-n-Hexyloxyphenyl) -1,3,4-oxadiazol-2-yl] benzoic acid IR (KBr): 2935, 2854, 1685, 1612, 1495, 1425, 1286, 1251 cm-1 '' '' NMR (DMSO-d6, δ): 0.89 (3H, t, J = 6.7Hz), 1.2-1.5 (6H, m), 1.6-1, 9 (3H, m), 4.12 (2H, t, J = 6.4Hz), 7.19 (2H, d, J = 8.7Hz), 8.08 (2H, d, J = 8, 7Hz), 8.18 (2H, d, J = 8.4Hz), 8.24 (2H, d, J = 8.4Hz) APCI MASS: m / z = 367 (M + H) + 1. Preparation 125,;, 4- [5- (4-n-Hexyloxyphenyl) -1,3,4-thiadiazol-2-yl] benzoic acid IR (KBr): 2952, 2586, 1699, 1604, 1517, 1432, 1251, 1174 cm -1 @ 1 H NMR (DMSO-d6, δ): 0.89 (3H, t, J = 6.7Hz), 1.3-1.9 (8H, m), 4.04 (-2H , t, J = 6.3Hz), 7.13 (2H, d, J = 8.8Hz), 7.97 (2H, d, J = 8.8Hz), 8.11 (4H, s) 50 APCI MASS: m / z = 383 (M + H) +.

Preparation 126 5- (4-Octyloxyphenyl) -1-methylpyrazole-3-carboxylic acid IR (KBr pellet): 2950, 2923, 1695, 1450, 1282, 1251, 956 cm -1 NMR (DMSO-d 6, δ):? , 86 (3H, t, J = 6.8Hz), 1.2-1.5 (10H, m), 1.6-1.8 (2H, m), 3.98 (2H, t, J = 6.5Hz), 4.10 (3H, s), 6.95 (1H, d, J = 8.8Hz), 7.18 (1H, s), 7.73 (2H, d, J = 8, 8Hz), 13.37 (1H, lev) APCI MASS: m / z = 331 (M + H +)

Preparation 127 4- [3- (4-n-Pentyloxy-phenyl) -pyrazol-5-yl] -benzoic acid IR (KBr): 3224, 2956, 1692, 1614, 1506, 1251 cm-1 NMR (DMSO-d6, δ): 0 , 91 (3H, t, J = 6.9Hz), 1.3-1.5 (4H, m), 1.6-1.8 (2H, m), 4.00 (2H, t, J = 6.5Hz), 7.02 (2H, d, J = 8.8Hz), 7.19 (III, s), 7.75 (2H, d, J = 8.8Hz), 7.95 (2H, d, J = 8.7Hz), 8.02 (2H, d, J = 8.7Hz), 12.8-13.3 (2H, lev) APCI MASS: m / z = 351 (M + H +)

Preparation 128 5- [4- (4-n-Butoxyphenyl) phenyl] furan-2-carboxylic acid IR (KBr): 2958, 2873, 1679, 1487, 1253, 1166 cm-1 NMR (DMSO-d6, δ): 0 , 95 (3H, t, J = 7.3Hz), 1.3-1.8 (4H, m), 4.02 (2H, 1.5H, J = 6.3Hz), 7.03 (2H , d, J = 8.6Hz, 7.17 (1H, d, J = 3.6Hz), 7.33 (1H, d, J = 3.6Hz), 7.66 (2H, d, J = 8.6Hz), 7.74 (2H, d, J = 8.4Hz), 7.86 (2H,; d, J = 8.4Hz), 13.1 (1H, lev s) V: APCI MASS: m / z = 337 (M + H) +

Preparation 129, 1 R 3- (S) -Hydroxyhexadecanoic acid; IR (KBr): 1679.7, 1467.6, 1224.6 cm -1 1 H NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.4Hz), 1.1-1.7 (24H, m), ppi 2.35-2.65 (2H, m), 4.03 (1H, m), 5.41 (1H, lev s)

Preparation 130 6- [4- (4-n-Hexyloxyphenyl) piperazin-1-yl] pyridazine-3-51 carboxylic acid IR (KBr): 1697.1, 1589.1, 1515.8, 1448.3 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.4Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 3 , 0-3.2 (4H, m), 3.7-4.0 (6H, m), 6.83 (2H, d, J = 9.0Hz), 6.95 (2H, d, J = 9.0Hz), 7.36 (1H, d, J = 9.6Hz), 7.86 (1H, d, J = 9.6Hz), 11.68 (1H, s)

Preparation 131 4- [4- [1- (4-n-Hexyloxyphenyl) piperidin-4-yl] piperazin-1-yl] benzoic acid hydrochloride IR (KBr): 1699.0, 1608.3, 1513.8 cm -1 (DMSO-d6, δ): 0.88 (3H, t, J = 6.5Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 2 , 0-2.45 (3H, m), 3.2-3.8 (12H, m), 3.94 (2H, t, J = 6.4Hz), 4.03 (2H, d, J = 11Hz), 6.95 (2H, d, J = 8.7Hz), 7.07 (2H, d, J = 8.9Hz), 7.32 (2H, lev s), 7.83 (2H, d) , J = 8.9Hz) APCI MASS: m / z = 466 (M + + H)

Preparation 132 6- (8-Methoxy-octyloxy) -2-naphthoic acid IR (KBr): 2937.1, 2854.1, 1677.8, 1211.1 cm -1 NMR (DMSO-d 6, δ): 1.2-1 , 6 (10H, m), 1.7-1.9 (2H, m), 3.20 (3H, s), 3.29 (2H, t, J = 6.5Hz), 4.11 (2H) , t, J = 6.4Hz), 7.23 (1H, dd, J = 9.0 and 2.3Hz), 7.39 (1H, d, J = 2.3Hz), 7.85 (1H, d, J = 8.7Hz, 7.93 (1H, d, J = 8.7Hz), 7.99 (1H, d, J = 9.0Hz), 8.51 (1H, s), 12 , 9 (1H, s) I ', Preparation 133' Mixture of (E) - and (Z) -3- [4- (4-Heptylphenyl) phenyl] -2-butenoic acid NMR (CDCl3, δ): 0.88 ( 3H, t, J = 6.6Hz), 1.15-1.50 (8H, m), 1.52-1.75; (2H, m), 2.63 and 3.62 (Total 3H, each s), 2.53-2.75 (2H, m), 6.24 and 5.68 (co. 1H, each s), 7.19-7.35 (2H, m), 7.47-7, 70 (6H, m) APCI MASS: m / z = 337 (M ++ 1), 351 (methyl ester ++ 1) 5 "I Preparation 134" d 3- [4- (4-Heptylphenyl) phenyl] propanoic acid: td NMR (CDCl3, δ): 0.88 (3H, t, J = 6.6Hz), 1.13-1.48 (8H, m), 1.48-1.75 (2H, m), 2 , 52-2.83 (4H, m), 3.00 (2H, t, J = 7.8Hz), 7.15-7.35 (4H, m), 7.40-7.60 (4H, m) 52 APCI MASS: m / z = 323 (M + -1).

Preparation 135 4- (4-n-Heptylphenyl) benzoylcarboxylic acid NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.6Hz), 1.13-1.50 (8H, m), 1.50. -1.75 (2H, m), 2.66 (2H, t, J = 7.7Hz), 7.20-7.40 (2H, m), 7.50-7.66 (2H, m) 7.66-7.84 (2H, m), 8.40-8.60 (2H, m) APCI MASS: m / z = 323 (M + -1).

Preparation 136 6-Hexylnaphthalene-2-carboxylic acid NMR (CDCl3, δ): 0.89 (3H, t, J = 6.8Hz), 1.15-1.53 (6H, m), 1.55-1. 84 (2H, m), 2.80 (2H, t, J = 7.6Hz), 7.42 (1H, dd, J = 1.7 and 8.4Hz), 7.67 (1H, s), 7.84 (1H, d, J = 8.6Hz), 7.90 (1H, d, J = 8.4Hz), 8.09 (1H, dd, J = 1.7 and 8.6Hz), δ , 68 (1H, s) APCI MASS: m / z = 257 (M + +1), 271 (methyl ester ++ 1).

Preparation 137 3- (E) - [4- [4- (7-Methoxy-heptyloxy) -phenyl] -phenyl] -acrylic acid NMR (DMSO-d6, δ): 1.20-1.60 (8H, m), 1.60- 1.83 (2H, m), 3.21 (3H, ·, s), 3.25-3.60 (2H, m), 4.01 (2H, t, J = 6.4Hz), δ , 54 (1H, d, J = 16.0Hz), 7.02 (2H, d, J = 8.8Hz), 7.55-7.80 (7H, m) APCI MASS: m / z = 369 (M + + 1) C "; Preparation 138

,., 3- (E) - [4- [4- (8-Methoxy-octyloxy) -phenyl] -phenyl] -acrylic acid IR

′ (KBr): 3037.3, 2933.2, 2858.0, 2551.4, 1706.7, 1677.8, 1629.6, 1602.6 cm -1: ¹H NMR (DMSO-d6, δ): 1.18-1.55 (10H, m), 1.65-1.83 (2H, m), 3.18-3.45: (5H, m), 4.01 (2H, t, J = 6.5Hz), 6.53 (1H, d, J = 16.0Hz), 7.02 (2H, d, J: 8.8Hz), 7.50-8.80 (7H, m) APCI MASS: m / z = 383 (M + +1),. Preparation 139 3 - (E) - [4- [4- (5-Hexenyloxy) phenyl] phenyl] acrylic acid NMR (DMSO-d 6, δ): 1.42-1.63 (2H, m), 1.63-1.85 (2H, m), 2.00-2.20 (2H, m), 4.03 (2H, t, J = 6.3Hz), 4.90-5.15 (2H) , m), 5.68-5, 97 (1H, 53m), 6.54 (1H, d, J = 16.7Hz), 7.02 (2H, d, J = 8.7Hz), 7.50- 7.80 (7H, m) APCI MASS: m / z = 323 (M + +1).

Preparation 140 3- (E) - [4- [4- (4-Methyl-pentyloxy) -phenyl] -phenyl] -acrylic acid IR (KBr): 2956.3, 2869.6, 2713.4, 2599.6, 1689.3, 1627 Δ, 1602.6 cm -1 NMR (DMSO-d6, δ): 0.89 (6H, d, J = 6.5Hz), 1.15-1.43 (2H, m), 1.48-. 1.90 (3H, m), 4.00 (2H, t, J = 6.7Hz), 6.54 (1H, d, J = 16Hz), 7.02 (2H, d, J = 8.7) H z), 7.50-7.90 (7H, m) APCI MASS: m / z = 325 (M + +1).

Preparation 141 3- (E) - [4- [4- (6-Fluoro-hexyloxy) -phenyl] -phenyl] -acrylic acid NMR (CDCl 3, δ): 1.39-2.00 (8H, m), 4.01 (2H, t, J = 6.5Hz), 4.47 (2H, dt, J = 47.3 and 6.0Hz), 6.49 (1H, d, J = 15.9Hz), 6.98 (2H, d , J = 8.7Hz), 7.40-7.70 (6H, m), 7.81 (1H, d, J = 15.9Hz) APCI MASS: m / z = 343 (M + +1).

Preparation 142; 3 - (E) - [4- [4- (6-Methoxyhexyloxy) phenyl] phenyl] acrylic acid NMR (DMSO-d 6, δ): 1.22-1.63 (6H, m), 1.63-1 , 88 (2H, m), 3.21 (3H,; v, s), 3.22-3.40 (2H, m), 4.00 (2H, t, J = 6.5Hz), 6, 54 (1H, d, J J = 15.8Hz), 7.02 (2H, d, J = 8.7Hz), 7.50-7.84 (7H, m) APCI MASS: m / z = 369 (methyl ester, M ++ 1)::: Preparation 143 4- [4- [8- (Tetrahydropyran-2-yloxy) octyloxy] phenyl] -: benzoic acid IR (KBr): 2935, 1697, 1683, 1604, 1303, 1290, 1197 cm-1 NMR (DMSO-d6, δ): 1.2-1.8 (18H, m), 3.3-3.9 (411, m), 4.01 (2H , t, J = 6.3Hz), 4.5-4.6 (1H, m), 7.03 (2H, d, J = 8.7Hz), 7.67 (2H, d, J = 8 , 7Hz), 7.74 (2H, d, J = 8.3Hz), 7.98 (2H, d, J = 8.3Hz), Γ APCI MASS: m / z = 425 (M-H +).

Preparation 144 4- [3- (4-n-Hexyloxyphenyl) pyrazol-5-yl] benzoic acid 54 IR (KBr): 2956, 2935, 1693, 1614, 1508, 1432, 1251, 1178 cm -1 1 H NMR (DMSO-d 6) , δ): 0.89 (3H, t, J = 6.4Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 4.00 (2H , t, J = 6.4Hz), 7.02 (2H, d, J = 8.7Hz), 7.12 (1H, s), 7.74 (2H, d, J = 8.7Hz), 7 , 95 (2H, d, J = 8.8Hz), 8.01 (2H, d, J = 8.8Hz), 13.17 (1H, s) APCI MASS: m / z = 365 (M + H +). )

Preparation 145 4- [4- [4- (6-Methoxy-hexyloxy) -phenyl] -phenyl] -benzoic acid IR (KBr): 2939, 2861, 1685, 1602, 1430, 1286, 1128 cm -1 NMR (DMSO-d 6, δ): 1.3-1.8 (8H, m), 3.21 (3H, s), 3.3-3.4 (2H, m), 4.01 (2H, t, J = 6.5Hz), 7.04 (2H, d, J = 8.6Hz), 7.66 (2H, d, J = 8.6Hz), 7.7-7.9 (6H, m), 8.03 (2H, d) , J = 8.2Hz) APCI MASS: m / z = 405 (M + H +)

Preparation 146 4- [5- (4- (8-Methoxy-octyloxy) -phenyl] -1,3,4-thiadiazol-2-yl] -benzoic acid IR (KBr): 2931, 2854, 1691, 1602, 1251 cm -1 DMSO-d 6, δ): 1.2-2.0 (12H, m), 3.20 (3H, s), 3.29 (2H, t, J = 6.4Hz), 4.04 (2H, t, J = 6.4Hz), 7.13 (2H, t, J = 8.8Hz), 7.9-8.2 (6H, m), 13.95 (1H, lev): "APCI MASS m / z = 441 (M + H +); 'Preparation 147 4- (4-n-Butoxyphenyl) cinnamic acid: IR (KBr): 2958, 2871, 1695, 1625, 1498, 1249 cm -1: NMR ( DMSO-d 6, δ): 0.94 (3H, t, J = 7.3Hz), 1.44 (2H, tq, J = 7.0 and 7.3Hz), 1.71 (2H, tt, J = 7.0 and 6.4Hz), 4.01 (2H, t, J = 6.4Hz), 6.54 (1H, d, J = 16.0Hz), 7.02 (2H, d, J = 8.7Hz), 7.6-7.9 (7H, m) APCI MASS: m / z = 297 (M + H +) ': Preparation 148 4- (5- (4-Cyclohexylphenyl) -1, 3,4-Thiadiazol-2-yl] benzoic acid IR (KBr): 2925, 2850, 1683, 1429, 1292 cm -1; ¹H NMR (DMSO-d 6, δ): 1.1-1.5 (5H) , m), 1.6-2.0 (5H, m), 2.4-2.6 (1H, m), 7.45 (2H, d, J = 8.3Hz), 7.96 (2H , d, J = 8.3Hz), 8.13 (4H, s) APCI MASS: m / z = 365 (M + H) +.

Preparation 149 55 4- [5- [4- (Piperidin-1-yl) phenyl] -1,3,4-thiadiazol-2-yl] -benzoic acid IR (KBr): 2931, 2854, 1685, 1604, 1415, 1238 cm -1 NMR (DMSO-d6, δ): 1.61 (6H, s), 3.31 (4H, s), 7.05 (2H, d, J = 9.0Hz), 7.83 ( 2H, d, J = 9.0Hz), 8.10 (4H, s) APCI MASS: m / z = 366 (M + H) +.

Preparation 150 4- [5- [4- [4-n-Propyloxyphenyl) phenyl] -1,3,4-oxadiazol-2-yl] benzoic acid IR (KBr): 2939, 1689, 1606, 1488, 1429, 1290 cm 1 H NMR (DMSO-d 6, δ): 1.00 (3H, t, J = 7.3Hz), 1.76 (2H, tq, J = 6.5 and 7.3Hz), 4.00 (2H , t, J = 6.5Hz), 7.07 (2H, d, J = 8.8Hz), 7.70 (2H, d, J = 8.5Hz), 7.78 (2H, d, J = 8.8Hz), 7.90 (2H, d, J = 8.5Hz), 8.0-8.4 (4H, m) APCI MASS: m / z = 401 (M + H) +.

Preparation 151 4- (5-n-Nonyl-1,3,4-oxadiazol-2-yl) benzoic acid IR (KBr): 2919, 2852, 1685, 1565, 1430, 1284 cm -1 NMR (DMSO-d 6, δ): 0.84 (3H, t, J = 6.5Hz), 1.2-1.5 (12H, m), 1.7-1.9 (2H, m), 2.94 (2H, t, J = 7.4Hz), 8.0-8.2 (4H, m), 13.35 (1H, '', s) APCI MASS: m / z = 317 (M + H +).

Preparation 152 "4- [3- (4-n-Hexyloxyphenyl) -1,2,4-oxadiazol-5-yl] benzoic acid h1: IR (KBr): 2942, 2869, 1695, 1421, 1251 cm -1 Nuclear Magnetic Resonance Spectrum (DMSO-d6, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.8 (8H, m), 4.06 (2H,. J = 6.5Hz), 7.13 (2H, d, J = 8.9Hz), 8.03 (2H, d, J = 8.9Hz), 8.17 (2H, d, J = 8 , 5Hz), 8.28 (2H, d, J = 8.5Hz) APCI MASS: m / z = 367 (M + H) +.

Preparation 153 4- [4- [4- (5-Methoxy-pentyloxy) -phenyl] -phenyl] -phenyl-acetic acid 56 IR (KBr): 2939, 2861, 1699, 1253, 1182, 1124 cm -1 NMR (DMSO-d 6, δ): 1 , 4.-1.9 (6H, m), 3.22 (3H, s), 3.39 (2H, t, J = 6.2Hz), 3.61 (2H, s), 4.01 (2H) , t, J = 6.4Hz), 7.02 (2H, d, J = 8.8Hz), 7.35 (2H, d, J = 8.2Hz), 7.6-7.8 (8H, m) APCI MASS: m / z = 405 (M + H +).

Preparation 154 4- [5- (4-n-Octyloxyphenyl) -1,3,4-thiadiazol-2-yl] benzoic acid IR (KBr): 2921, 2856, 1691, 1432, 1251 cm -1 NMR (DMSO-d , δ): 0.87 (3H, t, J = 6.7Hz), 1.2-1.5 (10H, m), 1.7-1.9 (2H, m), 4.07 (2H) , t, J = 6.5Hz), 7.13 (2H, d, J = 8.9Hz), 7.97 (2H, d, J = 8.9Hz), 8.12 (4H, s) APCI- MASS: m / z = 411 (M + H +)

Preparation 155 4- [5- (4-Trans-n-Pentylcyclohexyl) -1,3,4-thiadiazol-2-yl] benzoic acid IR (KBr): 2919, 2848, 1677, 1430, 1294 cm -1 1 H NMR (DMSO) -dg, δ): 0.87 (3H, t, J = 6.9Hz), 1.0-1.4 (11H, m), 1.5-1.6 (2H, m), 1.8 -2.0 (2H, m), 2.1-2.3 (2H, m), 3.1-3.3 (1H, m), 8.07 (4H, s): "APCI MASS: m / z = 359 (M + H +); Preparation 156 4- [3- (4-n-Pentyloxy-phenyl) -isoxazol-5-yl] -benzoic acid IR (KBr): 2925, 2869, 1699, 1687, 1612, 1432, 1251, 1178 cm -1: NMR (DMSO-d 6, δ ): 0.91 (3H, t, J = 6.9Hz), 1.2-1.5 (4H, m), 1.7-1.9 (2H, m), 4.04 (2H, t) , J = 6.5Hz), 7.09 (2H, d, J = 8.8Hz), 7.69 (1H, s), 7.85 (2H, d, J = 8.8Hz), 8.01 (2H, d, J = 8.5Hz), 8.11 (2H, d, J = 8.5Hz) APCI MASS: m / z = 352 (M + H +) +, Preparation 157 4- [5 - [4- (8-Methoxy-octyloxy) -phenyl] -1,3,4-oxadiazol-2, 1, 3-yl] benzoic acid: 1 H IR (KBr): 2967, 2937, 2877, 1687, 1290 cm -1 NMR (DMSO-d6, δ): 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3.20 (3H, s), 3.29 (2H, t, J = 6.4Hz), 4.08 (2H, t, J = 6.5Hz), 7.17 (2H, d, J = 8.9Hz), 57.07 (2H, d, J = 8.9Hz), 8.15 (2H, d, J = 8.6Hz), 8.24 (2H, d, J = 8.6Hz) APCI MASS: m / z = 425 (M + H) + - Preparation 158 4- [4- (6-Phenyl-pyridazin-3-yloxy) -phenyl] -benzoic acid IR (KBr): 1700, 1687, 1608, 1427, 1284, 1186 cm -1 NMR (DMSO-d 6, δ): 7.40 (2H, d, J = 8.6Hz), 7.5-7.7 (4H, m), 7.7-7.9 (4H, m), 7.9-8.1 (4H, m) , 8.35 (1H, d, J = 9 , 2Hz), 12.99 (1H, lev s) APCI MASS: m / z = 369 (M + H) +.

Preparation 159 4- [5- (4-n-Octyloxyphenyl) -1,3,4-oxadiazol-2-yl] benzoic acid IR (KBr): 2921, 2852, 1685, 1612, 1496, 1425, 1288, 1251 cm -1 1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz), 1.2-1.5 (10H, m), 1.7-1.9 (2H, m) , 4.08 (2H, t, J = 6.4Hz), 7.17 (2H, d, J = 8.7Hz), 8.07 (2H, d, J = 8.7Hz), 8.15 ( 2H, d, J = 8.5Hz), 8.24 (2H, d, J = 8.5Hz), 13.36 (1H, lev) APCI MASS: m / z = 395 (M + H +). 160; 1 H, 4- [2- (4-n-Hexyloxyphenyl) pyrimidin-6-yl] benzoic acid IR (KBr): 2944, 2863, 1697, 1585, 1415, 1386, 1253 cm -1; N, NMR (DMSO-d , δ): 0.89 (3H, t, J = 6.7Hz), 1.2-1.6 (6H, m), 1.7-1.9 ((2H, m), 4.07 ( 2H, t, J = 6.6Hz), 7.10 (2H, d, J = 8.9Hz), 8.00 (1H, d, J = 5.2Hz), 8.13 (2H, d) , J = 8.4Hz), 8.44 (2H, d, J = 5.9Hz), 8.47 (2H, d, J = 5.9Hz), 8.95 (1H, d, J = 5 , 2 Hz): APCI MASS: m / z = 377 (M + H +); ', Preparation 161 3.7 4- [4- (7-Piperidinocarbonylheptyloxy) phenyl] benzoic acid IR (KBr): 2933, 2858, 1697; 1677, 1637, 1604, 1429, 1249 cm -1 ('(1; NMR (DMSO-d 6, δ)): 1.2-1.8 (16H, m), 2.26 (2H, t, J = 7 , 5Hz), 3.2-3.5 (4H, m), 4.01 (2H, t, J = 6.4Hz), 7.03 (2H, d, J = 8.8Hz), 7.67 (2H, d, J = 8.8Hz), 7.74 (2H, d, J = 8.4Hz), 7.98 (2H, d, J = 8.4Hz) // APCI MASS: m / z = 424 (M + H +)

Preparation 162 58 6- [4- (4-n-Heptyloxyphenyl) piperazin-1-yl] nicotinic acid IR (KBr): 2929, 2854, 1695, 1673, 1606, 1577, 1515, 1421, 12 45 cm -1; DMSO-d6, δ): 0.86 (3H, t, J = 6.7Hz), 1.2-1.5 (8H, m), 1.6-1.8 (2H, m), 3, 0-3.2 (4H, m), 3.6-3.8 (4H, m), 3.87 (2H, t, J = 6.5Hz), 6.8-7.2 (5H, m) ), 7.95 (1H, dd, J = 8.9 and 2.3Hz), 8.62 (1H, d, J = 2.3Hz) APCI MASS: m / z = 398 (M + H +)

Preparation 163 6- [4- [4- (8-Methoxy-octyloxy) -phenyl] -piperazin-1-yl] -nicotinic acid IR (KBr): 2933, 2856, 1697, 1672, 1605, 1511, 1421, 1245 cm -1 NMR ( DMSO-d6, δ): 1.2-1.8 (12H, m), 3.08 (4H, t, J = 5.0Hz), 3.20 (3H, s), 3.28 (2H, t, J = 6.5Hz), 3.78 (4H, t, J = 4.6Hz), 3.87 (2H, t, J = 6.4Hz), 6.8-7.0 (5H, m ), 7.95 (1H, dd, J = 9.0 and 2.2Hz), 8.65 (1H, d, J = 2.2Hz), 12.54 (1H, s) APCI MASS: m / z = 442 (M + H +)

Preparation 164 ', 4- [5- [4- (4-n-Propyloxyphenyl) phenyl] -1,3,4-thiadiazol-2-yl] benzoic acid: IR (KBr): 1685, 1537, 1423 817 cm -1 NMR (DMSO-d 6, δ): 1.00 (3H, t, J = 6.7Hz), 1.6-1.8 (2H, m), 4.00 (2H, t, J = 6.6Hz), 7.0-7.2 (2H, d, J = 8.6Hz), 7.6-8.1 (10H, m) APCI MASS: m / z = 417 (M + H) +

Preparation 165 :; To a solution of ethyl 4- [5- (4-n-pentyloxy-phenyl) -isoxazol-3-yl] -benzoate (6.33 g) in ethanol (60 mL) and tetra-1 · 1 hydrofuran (90 mL) was added 2N aqueous sodium hydroxide solution (12.5 mL) at 80 ° C. The mixture was refluxed for 1 hour and poured into ice water. The suspension was adjusted to pH 2.0 with 1N HCl. The precipitate was collected by filtration, washed with water and dried to give 4- [5- (4-n-pentyloxy-phenyl) -isoxazol-3-yl] -benzoic acid (5.80 g).

IR (KBr): 2939, 2867, 1681, 1614, 1429, 1255, 1178, 821 cm -1 NMR (DMSO-d6, δ): 0.91 (3H, t, J = 7.1 Hz), 1.3 -1.5 (4H, m), 1.6-1.8 59 (2H, m), 4.04 (2H, t, J = 6.5Hz), 7.11 (2H, d, J = 8 , 9Hz), 7.54 (1H, s), 7.85 (2H, d, J = 8.9Hz), 7.98 (2H, d, J = 8.6Hz), 8.11 (2H, d) , J = 8.6Hz) APCI MASS: m / z = 352 (M + H) +

The following compounds (Preparations 166-170) were obtained in the same manner as Preparation 40.

Preparation 166 5- [4- (4-n-Hexyloxyphenyl) piperazin-1-yl] picolinic acid trihydrochloride IR (KBr): 1689.3, 1577.5, 1511.9, 1241.9 cm -1 NMR (DMSO- dg, δ): 0.88 (3H, t, J = 6.5Hz), 1.15-1.5 (6H, m), 1.6-1.8 (2H, m), 3.1-. 3.25 (4H, m), 3.45-3.6 (4H, m), 3.89 (2H, t, J = 6.4Hz), 6.84 (2H, d, J = 9.1Hz) ), 6.97 (2H, d, J = 9.1 Hz), 7.43 (1H, dd, J = 8.8 and 3.0 Hz), 7.90 (1H, dd, J = 8.8 and 0.7Hz), 8.41 (1H, dd, J = 3.0 and 0.7Hz) APCI MASS: m / z = 384 (M + + H)

Preparation 167 4- [4- (4-Phenylcyclohexyl) piperazin-1-yl] benzoic acid dihydrochloride IR (KBr): 1700.9, 1606.4, 1220.7, 1180.2 cm -1 NMR (DMSO-d δ): 1.4-1.85 (4H, m), 1.9-2.05 (2H, m), 2.2-2.4 (2H, m), 3.1-3.5 ( 6H, m), 3.5-3.7 (2H, m), 3.9-4.2 (2H, m), 7.06 (2H, d, J = 8.8Hz), 7.1 -7.4 (5H, m), 7.83 (2H, d, J = 8.8Hz) / APCI MASS: m / z = 365 (M + + H):. Preparation 168 4- (4-Trans-n-Pentylcyclohexyl) benzoic acid IR (KBr): 1681.6, 1423.2, 1290.1 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.6Hz), 1.0-1.6 (13H, m), 1.89 (4H, d, J = 10Hz), 2.54 (1H, t, J = 12Hz), 7.30 ( 2H, d, J = 8.3Hz), 8.03 (2H, ', d, J = 8.3Hz) APCI MASS: m / z = 274 (M + + H)': Preparation 169 4- ( 4-Piperidinopiperidin-1-yl) benzoic acid IR (KBr): 1710.6, 1403.9 cm -1 NMR (DMSO-d 6, δ): 1.6-2.1 (8H, m), 2.17 ( 2H, d, J = 12Hz), 2.7-3.05 60 (4H, m), 3.2-3.5 (1H, m), 3.35 (2H, d, J = 12Hz), 4 , 05 (2H, d, J = 13Hz), 7.01 (2H, d, J = 8.9Hz), 7.77 (2H, d, J = 8.9Hz), 10.84 (1H, s) APCI MASS: m / z = 289 (M + + H)

Preparation 170 3-Chloro-4- [4- (4-n-hexyloxyphenyl) piperazin-1-yl] -benzoic acid dihydrochloride IR (KBr): 1712.5, 1598.7, 1513.8, 1251.6 cm -1 DMSO-d6, δ): 0.88 (3H, t, J = 6.6Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 3, 4-3.6 (8H, m), 3.98 (2H, t, J = 6.4Hz), 7.02 (2H, d, J = 9.0Hz), 7.32 (1H, d, J = 8.1 Hz), 7.60 (2H, d, J = 9.0Hz), 7.89 (1H, d, J = 8.1Hz), 8.02 (1H, s) APCI MASS: m / z = 417 (M ++ H)

The following compounds (Preparations 171-175) were obtained in the same manner as Preparation 41.

Preparation 171

Ethyl [4- (4-octylphenyl) -2,3-dihydro-4H-1,2,4-triazol-3-one-2-yl] acetate IR (KBr): 2921.6, 1764.5, 1715 1197.6 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.7Hz), 1.30 (3H, t, J = 7.1Hz), 1.2-1 , 4 (10H, m), 1.5-1.7 (2H, m), 2.63 (2H, t, J = 7.9Hz), 4.26 (2H, q, J = 7, 1Hz), 4.64 (2H, s), 7.28 (2H, d, J = 8.4Hz), 7.44 (2H, d, J = 8.4Hz), 7.71 (1H, s) )

Preparation 172! 4- [4- (4-tert-Butoxycarbonylpiperazin-1-yl) phenyl] -2- (4-methylpentyl) -2,3-dihydro-4H-1,2,4-triazol-3-one IR ( KBr): 1687.4 cm -1 NMR (CDCl 3, δ): 0.90 (6H, d, J = 6.5Hz), 1.1-1.4 (2H, m), 1.49 (9H, s), 1.4-1.9 (3H, m), 3.16 (4H, t, J = 4.9Hz), 3.59 (4H, t, J = 4.9Hz), 3.82 ( 2H, t, J = 7.3Hz), 6.98 (2H, d, J = 9.0Hz), 7.41 (2H, d, J = 9.0Hz), 7.61 (1H, s)

Preparation 173 61

Methyl 6- (8-bromooctyloxy) -2-naphthoate IR (KBr): 2933.2, 2856, 1, 1720.2, 1294, 1209, 1 cm -1 NMR (CDCl 3, δ): 1.3-1 , 6 (8H, m), 1.75-2.0 (4H, m), 3.42 (2H, t, J = 6.8Hz), 3.96 (3H, s), 4.09 (2H) , t, J = 6.5Hz), 7.14 (1H, d, J = 1.7Hz), 7.19 (1H, dd, J = 8.9 and 1.7Hz), 7.73 (1H, d, J = 8.7Hz), 7.83 (1H, d, J = 8.9Hz), 8.01 (1H, dd, J = 8.7 and 1.7Hz), 8.51 (1H, d , J = 1.7Hz) APCI MASS: m / z = 393 (M + + H)

Preparation 174 4- [4- (6-n-Propyloxyhexyloxy) phenyl] benzoic acid IR (KBr): 2937, 2858, 1695, 1683, 1604, 1430, 1290, 1247, 1195 cm -1 NMR (DMSO-d6, δ) 0.85 (3H, t, J = 7.4Hz), 1.3-1.9 (10H, m), 3.2-3.4 (4H, m), 4.01 (-2H, t , J = 6.3Hz), 7.04 (2H, d, J = 8.7Hz), 7.67 (2H, d, J = 8.7Hz), 7.74 (2H, d, J = 8 , 3Hz), 7.98 (2H, d, J = 8.3Hz), 12.9 (1H, s) APCI MASS: m / z = 357 (M + H +)

Preparation 175; ', 4- [4- (6-Bromohexyloxy) phenyl] bromobenzene NMR (CDCl 3, δ): 1.40-1.65 (4H, m), 1.70-2.00 (4H, m) , 3.43 (2H, t, Y, J = 6.7Hz), 4.00 (2H, t, J = 6.4Hz), 6.95 (2H, d, J = 8.8Hz) , 7.30-7.60 '(6H, m)

The following compounds (Preparations 176-180) were obtained in the same manner as Preparation 43.

Preparation 176 ... 4- [4- (4-n-Pentyloxy-phenyl) -piperazin-1-yl] -benzoic acid dihydrochloride Y ': IR (KBr): 1668.1, 1602, 6, 1510, 0, 1228.4 cm -1 NMR (DMSO-d6, δ): 0.89 (3H, t, J = 6.9Hz), 1.2-1.5 (5H, m), 1.6-1.9 (2H, m), 3.0-3.2 (4H, m), 3.4-3.6 (4H, m), 3.88 (2H, t, J = 6.4Hz),? 6.83 ( 2H, d, J = 9Hz), 6.9-7.1 (4H, m), 7.79 (2H, d, J = 8.8Hz), 12.32: Y! uh, s) APCI MASS: m / z = 369 (M + H +)

Preparation 177 62 4- [4- (4-n-Heptyloxyphenyl) piperazin-1-yl] benzoic acid dihydrochloride IR (KBr): 1666.2, 1600.6, 1511.9 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.9Hz), 1.2-2.0 (10H, m), 3.1-3.3 (4H, m), 3.4-3.6 (4H , m), 3.92 (2H, t, J = 6.4Hz), 6.8-7.1 (6H, m), 8.00 (2H, d, J = 8.8Hz)

Preparation 178 4- [4- [4- (4-Methyl-pentyloxy) -phenyl] -piperazin-1-yl] -benzoic acid dihydrochloride IR (KBr): 1668.1, 1602.6, 1510.0, 1236.1 cm -1 NMR (DMSO-d6, δ): 0.89 (6H, d, J = 6.5Hz), 1.2-1.4 (2H, m), 1.4-1.8 (3H, m), 3 , 0-3.2 (4H, m), 3.3-3.5 (4H, m), 3.87 (2H, t, J = 6.3Hz), 6.83 (2H, d, J = 9.0Hz), 6.9-7.1 (4H, m), 7.79 (2H, d, J = 8.8Hz), 12.33 (1H, s) APCI MASS: m / z = 383 (M + H +)

Preparation 179 4- [4- [4- (8-Bromooctyloxy) -phenyl] -piperazin-1-yl] -benzoic acid dihydrochloride IR (KBr): 1670.1, 1602.6, 1511.9, 1234.2 cm -1 DMSO-d6, δ): 1.2-1.5 (8H, m), 1.6-1.9 (4H, m), 3.0-3.2 (4H, m), 3.2- 3.5 (4H, m), 3.52 (2H, t, J = 6.7Hz), 3.88 (2H, t, J = 6.4Hz), 6.83; (2H, d, J = 9.1Hz), 6.94 (2H, d, J = 9.1Hz), 7.02 (2H, d, J = 8.9Hz), 7.79 (2H, d, J = 8.9Hz) Preparation 180 1,3-Fluoro-4- [4- (4-n-hexyloxyphenyl) piperazin-1-yl] -benzoic acid dihydrochloride IR (KBr): 1673.9, 1511.9, 1240 0 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.5Hz), 1.2-1.5 (6H, m), 1.6-1.8: "! (2H, m), 3.0-3.5 (8H, m), 3.88 (2H, t, J = 6.4Hz), 6.7-7.2 (5H, m), 7.4 -7.8 (2H, m), 12.82 (1H, s) APCI MASS: m / z = 401 (M + + H)

The following compound was obtained in the same manner as Preparation 46.

Preparation 181 63 1- (4-Methoxycarbonylphenyl) -3- (4-n-hexyloxyphenyl) -propane-1,3-dione IR (KBr): 2956, 2927, 2856, 1722, 1511, 1284, 1108 cm -1 (CDCl 3, δ): 0.92 (3H, t, J = 6.4Hz), 1.2-2.0 (8H, m), 3.96 (3H, s), 4.04 (2H, t) , J = 6.5Hz), 6.82 (1H, s), 6.97 (2H, d, J = 8.7Hz), 7.9-8.1 (4H, m), 8.14 (2H , d, J = 8.3Hz) APCI MASS: m / z = 383 (M + H +)

The following compounds (Preparations 182-185) were obtained in the same manner as Preparation 47.

Preparation 182

Methyl 5- (4-octyloxyphenyl) -1-methylpyrazole-3-carboxylate IR (KBr pellet): 2923, 1724, 1616, 1513, 1446, 1251, 1120 cm-1 · NMR (CDCl3, δ): 0 , 89 (3H, t, J = 6.8Hz), 1.2-1.5 (10H, m), 1.7-1.9 (2H, m), 3.90 (3H, s), 3 , 98 (2H, t, J = 6.6Hz), 4.20 (3H, s), 6.92 (2H, d, J = 8.9Hz), 7.04 (1H, s), 7.89 (2H, d, J = 8.9Hz) APCI MASS: m / z = 345 (M + H +); 1, Preparation 183, '' Methyl 4- [5- (4-n-pentyloxy-phenyl) -pyrazol-3 -yl] benzoate, δ: IR (KBr): 3236, 2952, 2873, 1716, 1616, 1508, 1276, 1174, δ; 1 H NMR (CDCl 3, δ): 0.94 (3H, t, J = 7.0Hz), 1.3-1.5 (4H, m), 1.7-1.9 (2H) , m), 3.92 (3H, s), 3.96 (2H, t, J = 6.7Hz), 6.78 (1H, s), 6.88 (2H, d, J = 8 , 7Hz), 7.55 (2H, d, J = 8.7Hz), 7.79 (2H, d, J = 8.4Hz), 8.02 (2H, d, J = 8.4Hz); APCI MASS: m / z = 365 (M + H +) -; Preparation 184 ':' ': Methyl 5- (4-octyloxyphenyl) isoxazole-3-carboxylate IR (KBr pellet): 2950, 2921, 1724, 1614, 1510, 1446, 1257, 1178, 1143, 1009 cm 1 H NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.6 (10H, m), 1.7-1.9 (2H, m) ), 4.0-4.1 (5H, m), 6.80 (1H, s), 6.98 (2H, dd, J = 6.9 and 2.1Hz), 7.73 (2H, dd) , J = 6.9 and 2.1Hz) 64 APCI MASS: m / z = 332 (M + H +)

Preparation 185

Methyl 4- [3- (4-n-hexyloxyphenyl) pyrazol-5-yl] benzoate IR (KBr): 2952, 1716, 1616, 1508, 1276, 1106 cm -1 NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.3Hz), 1.2-1.6 (6H, m), 1.7-1.9 (2H, m), 3.8-4.0 (5H, m) , 6.76 (1H, s), 6.86 (2H, d, J = 8.8Hz), 7.54 (2H, d, J = 8.8Hz), 7.77 (2H, d, J = 8.4Hz), 8.00 (2H, d, J = 8.4Hz) APCI MASS: m / z = 379 (M + H +)

Preparation 186

A suspension of 1- (4-n-pentyloxyphenyl) -3- (4-ethoxycarbonylphenyl) -1-buten-3-one (74.43 g) and hydroxyamine hydrochloride (28.23 g) and potassium carbonate ( 56.11 g) in ethanol (400 ml) was refluxed for 4 hours. The mixture was diluted with ethyl acetate, washed with water (x 2), brine and dried over magnesium sulfate. The solvents were removed under reduced pressure to give the crude oxime. To a solution of the crude oxime in dichloroethane (500 mL) was added activated manganese (IV) oxide (200 g). The reaction mixture was refluxed for 2 hours and filtered. The residue was washed with dichloromethane. The solvents were removed under reduced pressure and the residue was triturated with acetonitrile. The solid was collected by filtration and dried to yield. Ethyl 4- [5- (4-n-pentyloxy-phenyl) -isoxazol-3-. yl] benzoate (21.07 g).

IR (KBr): 2945, 2872, 1717, 1615, 1508, 1280, 1108 cm -1 NMR (CDCl 3, δ): 0.95 (3H, t, J = 6.9Hz), 1.3 1.9 (9H, m), 4.01 (2H, t, J = 6.5 Hz), 4.41 (2H, q, J = 7.1 Hz), 6.74 (1H, s), 6.99 (2H, d, J = 8.8Hz), 7.76 (2H, d, J = 8.8Hz), 7.93 (2H, d, J = 8.4Hz), 8.15 ( 2H, d, J = 8.4Hz) t, APCI MASS: m / z = 380 (M + H +). 11 The following compounds (Preparations 187-190) were obtained in a manner similar to Preparation 48.

Preparation 187. : Methyl 6- [4- (4- (8-methoxyoctyloxy) phenyl] piperazin-1'-yl] nicotinate IR (KBr): 2933, 2858, 1722, 1608, 1513, 1432, 1405, 1278, 1245 cm - NMR (CDCl 3, δ): 1.3-1.9 (12H, m), 3.16 (4H, t, J = 5.0Hz), 3.33 (3H, 65 s), 3.36 ( 2H, t, J = 6.5Hz), 3.8-4.0 (9H, m), 6.64 (1H, d, J = 9.1Hz), 6.85 (2H, d, J = 9) , 2Hz), 6.93 (2H, d, J = 9.2Hz), 8.04 (1H, dd, J = 9.1 and 2.2Hz), 8.81 (1H, d, J = 2, 2Hz) APCI MASS: m / z = 456 (M + H +)

Preparation 188 4- [4- (5-Methoxypentyloxy) phenyl] bromobenzene IR (KBr): 2940, 2856, 1604, 1479, 1286, 1255, 1124 cm -1 NMR (CDCl 3, δ): 1.5-1.9 (6H, m), 3.34 (3H, s), 3.41 (2H, t, J = 6.1Hz), 3.99 (2H, t, J = 6.4Hz), 6.95 (2H) , d, J = 8.7Hz), 7.4-7.6 (6H, m) APCI MASS: m / z = 349 (M + H +)

Preparation 189

Methyl 6- (8-methoxyoctyloxy) -2-naphthoate NMR (DMSO-d6, δ): 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3 20 (3H, s), 3.29 (2H, t, J = 6.4Hz), 3.89 (3H, s), 4.11 (2H, t, J = 6.4Hz), 7.24 ( 1H, dd, J = 9.0 and 2.4Hz), 7.40 (1H, d, J = 8.7Hz), 7.88 (1H, d, J = 8.7Hz), 7.94 (1H , dd, J = 8.7 and 1.5Hz), 8.03 (1H, d, J = 9.0Hz), 8.55 (1H, d, J = 1.5Hz), ', Preparation 190' '4- [4- [4- (8-Methoxy-octyloxy) -phenyl] -piperazin-1-yl] - ?, benzoic acid dihydrochloride IR (KBr): 1668.1, 1602.6, 1511.9, 1236.1 cm -1 NMR (DMSO-d6, δ): 1.2-1.8 (12H, m), 3.05-3.2 (4H, m), 3.29 (2H, t, J = 7.1Hz), 3.33 (3H, s), 3.4-3.55 (4H, m), 3.88 (2H, t, J = 6.4Hz), 6.82 (2H, d, J = 9.0Hz) ), 6.94 (2H, d, J = 9.0Hz), 7.02 (2H, d, J = 8.8Hz), 7.79 (2H, d, J = 8.8Hz), 12.31 (1H, s)

The following compounds (Preparations 191-254) were obtained in a similar manner; _ · As a preparation 49.

• Preparation 191 1- [4- [4- [4- [2- (4-Methylpentyl) -2,3-dihydro-4H-1,2,4-triazol-3-one-4-yl] phenyl] piperazine -1-yl] benzoyl] benzotriazole-3-oxide 66 IR (KBr): 1766.5, 1693.2, 1600.6, 1519.6 cm -1 Preparation 192 1- [4- (4-Octylphenyl) -2 , 3-Dihydro-4H-1,2,4-triazol-3-one-2-ylacetyl] benzotriazole-3-oxide IR (KBr): 2921.6, 1753.0, 1720.0, 1423.2 cm- 1 NMR (CDCl 3, δ): 0.88 (3Ή, t, J = 6.7Hz), 1.2-1.4 (10H, m), 1.5-1.8 (2H, m), 2 , 65 (2H, t, J = 7.5Hz), 5.46 (2H, s), 7.30 (2H, d, J = 8.5Hz), 7.48 (2H, d, J = 8, 5Hz), 7.62 (1H, t, J = 8.3Hz), 7.80 (1H, s), 7.82 (1H, t, J = 8.3Hz), 8.05 (1H, d, J = 8.3Hz), 8.37 (1H, d, J = 8.3Hz)

Preparation 193 1- [4- [4- [4- (7-Methoxy-heptyloxy) -phenyl] -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1783.8, 1600.6, 1511.9 , 1232.3, 1184.1 cm -1 NMR (CDCl 3, δ): 1.3-1.9 (10H, m), 3.2-3.3 (4H, m), 3.34 (3H, s), 3.38 (2H, t, J = 6.4Hz), 3.5-3.7 (4H, m), 3.92 (2H, t, J = 6.5Hz), 6.87 ( 2H, d, J = 9.2Hz), 6.95 (2H, d, J = 9.2Hz), 7.00 (2H, d, J = 9.0Hz), 7.3-7.6 (3H, m ), 8.09 (1H, d, J = 8.2Hz), 8.15 (2H, d, J = 9.0Hz)

Preparation 194 '1- (4- [4- (4-n-Heptyloxyphenyl) piperazin-1-yl] benzoyl] -N: benzotriazole-3-oxide 1H-IR (KBr): 1783.8, 1600.6, 1511 9, 1230.4, 1184.1 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6, 3Hz), 1.2-1.6 (8H, m), 7-1.9 (2H, 7, m), 3.2-3.3 (4H, m), 3.5-3.7 (4H, m), 3.93 (2H, t, J = 6 , 5Hz), 6.87 (2H, d, J = 9.2H), 6.95 (2H, d, J = 9.2Hz), 7.00 (2H, d, J = 9.0Hz), 7 , 3-v '7.7 (3H, m), 8.09 (1H, d, J = 8.2Hz), 8.15 (2H, d, J = 9.0Hz) •'; Preparation 195 '; · 1- [4- [4- [4- (4-Methyl-pentyloxy) -phenyl] -piperazin-1-yl] -; benzoyl] -benzotriazole-3-oxide NMR (CDCl3, δ): 0.92 (6H, d , J = 6.6Hz), 1.2-1.4 (2H, m), 1.5-1.9 (3H, m), 3.1-3.3 (4H, m), 3.5 -3.7 (4H, m), 3.92 (2H, t, J = 6.6Hz), 6.87 .I (2H, d, J = 9.3Hz), 6.96 (2H). , d, J = 9.3Hz), 7.01 (2H, d, J = 9.0Hz), 7.4-7.6 (3H, m), 8.10 (1H, d, J = 8.2Hz) , 8.15 (2H, d, J = 9.0Hz)

Preparation 196 67 1- [4- [4- (4-n-Pentyloxy-phenyl) -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1787.7, 1600.6, 1511.9, 1232.3, 1184.1 cm -1 NMR (CDCl 3, δ): 0.93 (3H, t, J = 6.9Hz), 1.3-1.6 (4H, m), 1.7-1. , 9 (2H, m), 3.1-3.4 (4H, m), 3.5-3.8 (4H, m), 3.93 (2H, t, J = 6.6Hz), 6 , 87 (2H, d, J = 9.2Hz), 6.92 (2H, d, J = 9.2Hz), 7.01 (2H, d, J = 9.1Hz), 7.4-7, Δ (3H, m), 8.10 (1H, d, J = 8.2Hz), 8.15 (2H, d, J = 9.1Hz)

Preparation 197 1- [4- [4- [8- (1H-Tetrazol-1-yl) octyloxy] phenyl] benzoyl] -benzotriazole-3-oxide and 1- [4- [4- [8- (2H-tetrazole) -2-yl) octyloxy] phenyl] benzoyl] benzotriazole-3-oxide IR (KBr): 1778.0, 1602.6, 1189.9, 981.6 cm -1 NMR (CDCl 3, δ): 1, 2-1.6 (8H, m), 1.7-1.9 (2H, m), 1.9-2.2 (2H, m), 4.02 (2H, t, J = 6.4Hz) ), 4.44 and 4.66 (2H, t, J = 7.1Hz), 7.02 (2H, d, J = 8.8Hz), 7.4-7.6 (3H, m), 7 , 63 (2H, d, J = 8.8Hz), 7.79 (2H, d, J = 8.6Hz), 8.12 (1H, d, J = 8.2Hz), 8.32 (2H, d, J = 8.6Hz), 8.51 and 8.60 · · (1H, s),. Preparation 198 1- [4- [4- [8- (2,6-Dimethylmorpholine-4-) yl) octyloxy] phenyl] -?, benzoyl] benzotriazole-3-oxide IR (KBr): 1778.0, 1600.6, 977.7 cm -1 NMR (CDCl 3, δ): 1.18 (6H, d , J = 6.3Hz), 1.2-1.7 (10H, m), 1.7-2.0 (4H, m), 2.4-2.6 (2H, m), 2.9 -3.2 (2H, m), 3.7-3.9 (2H, m), 4.01: (2H, t, J = 6.5Hz), 7.02 (2H, d, J = 8.8Hz), 7.4-7.7 (3H, m), 7.63 (2H, d, J = 8.8Hz), 7.79 (2H, d, J = 8.5Hz), 8, 12 (1H, d, J = 8.1Hz), 8.32 (2H, * '> d, J = 8.5Hz) 1' '1- [6- [4- (4-octyloxyphenyl) piperazin-l-yl] nicotinoyl] - \; benzotriazole-3-oxide IR (KBr pellet): 2922, 2854, 1766, 1602, 1513, 1417, 1234, 1025, 950, 813 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.5 (10H, m), 1.7-1.9 68 (2H, m), 3.1-3.3 (4H, m), 3.9- 4.1 (6H, m), 6.75 (1H, d, J = 9.2Hz), 6.87 (2H, d, J = 9.2Hz), 6.95 (2H, d, J) = 9.2Hz), 7.4-7.6 (3H, m), 8.10 (1H, d, J = 8.1Hz), 8.19 (1H, dd, J = 9.2 and 2, 4Hz), 9.04 (1H, d, J = 2.4Hz) APCI MASS: m / z = 529 (M + H +)

Preparation 200 1- [2- (4-Hexyloxyphenyl) -benzoxazol-5-ylcarbonyl] -benzotriazole-3-oxide IR (KBr): 2950, 1774, 1623, 1501504, 1265, 1176 cm-1 NMR (CDCl3, δ) 0.93 (3H, t, J = 6.9Hz), 1.3-1.6 (6H, m), 1.8-2.0 (2H, m), 4.07 (2H, t, J = 6.5Hz), 7.06 (2H, d, J = 8.9Hz), 7.4-7.6 (3H, m), 7.75 (1H, d, J = 8.6Hz), 8.13 (1H, d, J = 8.2Hz), 8.2-8.4 (3H, m), 8.67 (1H, d, J = 1.6Hz) APCI MASS: m / z = 457 (M + H +)

Preparation 201 1- [4- [4- (4-n-Butyloxyphenyl) phenyl] benzoyl] benzotriazole-3-oxide IR (KBr): 2958, 2871, 1776, 1600, 1398, 1255, 1211, 1037 cm -1 1 H NMR (CDCl 3, δ): 1.00 (3H, t, J = 7.2Hz), 1.4-1.9 (4H, m), 4.03 (2H, t, J = 6, 4Hz), 7.01 (2H, d, J = 8.3Hz), 7.4-7.8 (9H, m), 7.87 (2H, d, J = 8.1Hz), 8.12 ( 1 H, d, J = 8.4Hz), 8.36 (2H, d, J = 7.9Hz):? APCI MASS: m / z = 464 (M + H) + 1 Preparation 202 1- [2- (4-Heptyloxyphenyl) pyridin-5-ylcarbonyl] benzotriazole-3-oxide δ IR (KBr): 2944, 2867, 1793, 1770, 1589, 1471, 1321, 1093 cm -1 NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.7Hz), 1.2-1.6 (8H, m), 1.7-1.9 (2H, m), 4.05 (2H, t, J = 6.5Hz), 7.04 (2H, d, J = 8.0Hz), 7.4-7.6 (3H, m), 7.91 (1H, d, J = 8.5Hz), δ , 1-8.2 (3H, m), 8.51 (1H, dd, J = 8.5 and V, 2.3Hz), 9.47 (1H, d, J = 2.3Hz) APCI MASS : m / z = 431 (M + H +)

Preparation 203 1- [2- (2-Octyloxypyridin-5-yl) benzoxazol-5-ylcarbonyl] benzotriazole-3-oxide IR (KBr pellet): 2925, 2854, 1787, 1623, 1479, 1263, 989 cm -1 1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.5 (10H, m), 1.8-1.9 (2H, m) , 4.42 (2H, t, J = 6.7Hz), 6.91 (1H, d, J = 8.7Hz), 6.4-6.6 (3H, m), 7.79 (1H, d, J = 8.6Hz), 8.13 (1H, d, J = 8.2Hz), 8.32 (1H, dd, J = 8.6 and 1.7Hz), 8.41 (1H, dd) , J = 8.7 and 2.4Hz), 8.70 (1H, d, J = 1.4Hz), 9.07 (1H, d, J = 1.9Hz) APCI MASS: m / z = 486 (M + H +)

Preparation 204 1- [2- [4- (4-Hexylphenyl) phenyl] benzoxazol-5-ylcarbonyl] benzotriazole-3-oxide IR (KBr): 2927, 2854, 1785, 1621, 1490, 1261, 1166, 1052 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.2-1.8 (8H, m), 2.68 (2H, t, J = 7, 9Hz), 7.31 (2H, d, J = 8.2Hz), 7.4-7.7 (5H, m), 7.79-7.81 (3H, m), 8.13 (1H, d, J = 8.3Hz), 8.3-8.4 (3H, m), 8.73 (1H, d, J = 1.3Hz) APCI MASS: m / z = 517 (M + H +)

Preparation 205 1- [2- [4- (4-n-Butyloxyphenyl) phenyl] pyridin-5-ylcarbonyl] benzotriazole-3-oxide IR (KBr): 2956, 2933, 2871, 1774, 1650, 1591, 1471 1251 cm -1 NMR (CDCl 3, δ): 1.00 (3H, t, J = 7.2Hz), 1.5-1.9 (4H, m), 4.03 (2H, t ,; , J = 6.4Hz, 7.02 (2H, d, J = 8.6Hz), 7.4-7.6 (3H, m), 7.54 (2H, d, J = 7, 3Hz), 7.62 (2H, d, J = 8.5Hz), 8.02 (1H, d, J = 8.3Hz), 8.13 (1H, d, J = 8.2Hz), 8, 21 (2H, d, J = 7.9Hz), 8.57 (1H, dd, J = 8.3 and 2.0Hz), 9.54 (1H, d, J = 2.0Hz) APCI MASS: m / z = 465 (M + H) + '' Preparation 206, 1- [4- [4- (5-Phenoxy-pentyloxy) -phenyl] -benzoyl] -benzotriazole-3 '->' oxide! IR (KBr): 2944, 2869, 1770, 1600, 1494, 1249, 1189 cm -1 NMR (CDCl 3, δ): 1.6-1.8 (2H, m), 1.8-2.0 (4H, m) ), 4.01 (2H, t, J · 6.3Hz), 4.07 (2H, t, J = 6.2Hz), 6.91 (2H, d, J = 8.9Hz) , 7.04 (2H, d, J: 8.7Hz), 7.3-7.6 (4H, m), 7.63 (2H, d, J = 8.6Hz), 7.78 ( 2H, d, J = 8.4Hz), 8.12 (1H, d, J = 8.4Hz), 8.32 (2H, d, J = 8.4Hz) APCI MASS: m / z = 494 ( M + H) +

Preparation 207 70 1- [4- [5- (4-Hexyloxyphenyl) -1,3,4-oxadiazol-2-yl] benzoyl] -benzotriazole-3-oxide IR (KBr): 2956, 2921, 2856, 1778 , 1612, 1496, 1261, 1232, 1025 cm -1 NMR (CDCl 3, δ): 0.92 (3H, t, J = 6.7Hz), 1.3-1.6 (6H, m), 8-2.0 (2H, m), 4.05 (2H, t, J = 6.5Hz), 7.05 (2H, d, J = 8.7Hz), 7.4-7.6 (3H , · M), 8.10 (2H, d, J = 8.7Hz), 8.13 (1H, d, J = 7.4Hz), 8.37 (2H, d, J = 8.5Hz), 8.45 (2H, d, J = 8.5Hz) APCI MASS: m / z = 484 (M + H) +.

Preparation 208 1- [4- [5- (4-n-Hexyloxy-phenyl) -1,3,4-thiadiazol-2-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 2952. 2873, 1774, 1602, 1261, 1230, 1176 cm -1 NMR (CDCl 3, δ): 0.93 (3H, t, J = 6.8Hz), 1.3-2.0 (8H, m), δ , 04 (2H, t, J = 6.5Hz), 7.02 (2H, d, J = 8.7Hz), 7.4-7.7 (3H, m), 7.98 (2H, d, J = 8.7Hz), 8.13 (1H, d, J = 8.7Hz), 8.25 (2H, d, J = 8.3Hz), 8.41 (2H, d, J = 8.3Hz) ) APCI MASS: m / z = 500 (M + H) +: 1, Preparation 209 1- [5- (4-O-oxy-oxyphenyl) -1-methylpyrazol-3-ylcarbonyl; 1 H] benzotriazole-3-oxide ":" δ IR (KBr pellet): 2939, 2852, 1776, 1687, 1612, 1448, 1249, 995 cm -1: 1 NMR (CDCl 3, δ): 0.89 ( 3H, t, J = 6.7Hz), 1.3-1.5 (10H, m), 1.7-1.9 (2H, m), 4.01 (2H, t, J = 6.5Hz) ), 4.25 (3H, s), 6.97 (2H, d, J = 6.8Hz), 7.4-7.7 (4H, m), 7.78 (2H, d, J = 6) , 8Hz), 8.14 (1H, d, J = 8.0Hz) APCI MASS: m / z = 448 (M + H +), ·, Preparation 210 1- [4- [5- (4-n- Pentyloxyphenyl) pyrazol-3-yl] benzoyl] -1,1-benzotriazole-3-oxide ·,; IR (KBr): 3251, 2956, 2869, 1780, 1612, 1506, 1232, 985 cm -1: NMR (CDCl 3, δ): 0.95 (3H, t, J = 6.9Hz), 1.3 1.6 (4H, m), 1.7-2.0 (2H, m), 4.01 (2H, t, J = 6.6Hz), 6.90 (1H, s), 6.99 ( 2H, d, J = 8.7Hz), 7.4-7.6 (5H, m), 8.0-8.2 (3H, m), 8.33 (2H, d, J = 8.4Hz) ) 71 APCI MASS: m / z = 468 (M + H +)

Preparation 211 1- [5- [4- (4-n-Butoxyphenyl) phenyl] furan-2-ylcarbonyl] -benzotriazole-3-oxide IR (KBr): 2958, 2871, 1781, 1678, 1603, 1535, 1479, 1265 cm -1 NMR (CDCl 3, δ): 1.00 (3H, t, J = 7.3Hz), 1.4-1.9 (4H, m), 4.02 (2H, t, J = 6 , 4Hz), 6.9-7.1 (3H, m), 7.4-8.2 (11H, m) APCI MASS: m / z = 351 (methyl ester)

Preparation 212 1- (3- (S) -Hydroxy-2-benzylhexadecanoyl) benzotriazole-3-oxide IR (pure): 2854.1, 1814.7, 1459.8, 742.5 cm -1 Preparation 213 1- ( 3- (R) -Benzyloxycarboxylamino-18-methoxyoctadecanoyl-1-benzotriazole-3-oxide IR (KBr): 1805, 0, 1729, 8, 1695, 1 H NMR (DMSO-d6, δ): 1.1-1 , 65 (30H, m), 3.20 (3H, s), 3.28 (2H, t, J = 6.5Hz), 4.01 (1H, m), 5.06 (2H, s), 7.32 (5H, m), 7.4-7.8 (3H, m), 8.12 (1H, d, J = 7Hz)! 1: Preparation 214, 1- (3- (S) -Hydroxyhexadecanoyl) -benzotriazole-3-oxide 1 H, IR (KBr): 1710, 6, 1498.4, 1429, 0.771, 4 cm -1. CDCl 3, δ): 0.88 (3H, t, J = 6.4Hz), 1.2-1.7 (24H, m), 2.00 (1H, s), 3.1-3.5 ( 2H, m), 4.30 (1H, m), 7.59 (1H, t, J = 7.8Hz), 7.81 (1H, t, J = 7.8Hz), 8.02 (1H, d, J = 8.3Hz), 8.42 1 (1H, d, J = 8.3Hz)! Preparation 215; · 1- (3-Methyl-2-tridecenoyl) -benzotriazole-3-oxide IR (KBr): 2927, 4, 1791.5, 1633, 4, 1081.9 cm -1: NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.3Hz), 1.1-1.7 (20H, m), 2.25 (3H, '), 6.08 (1H, s), 7 , 3-7.6 (3H, m), 8.06 (1H, d, J = 8.2Hz)

Preparation 216 72 1- [4- [4- [4- (8-Methoxy-octyloxy) -phenyl] -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1780.0, 1600.6, 1511, 9, 1234.2, 1184.1 cm -1 NMR (CDCl 3, δ): 1.3-1.9 (12H, m), 3.24 (4H, t, J = 5.0Hz), 3.33 (3H, s), 3.37 (2H, t, J = 6.8Hz), 3.62 (4H, t, J = 5.0Hz), 3.92 (2H, t, J = 6.5Hz) , 6.8-7.1 (6H, m), 7.35-7.65 (3H, m), 8.09 (1H, d, J = 8.2Hz), 8.15 (2H, d, J = 9.0Hz)

Preparation 217 1- [3-Fluoro-4- [4- (4-n-hexyloxy-phenyl) -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1778.0 cm -1 [3-Chloro-4- [4- (4-n-hexyloxyphenyl) piperazin-1-yl] benzoyl] benzotriazole-3-oxide IR (KBr): 1778.0, 1594.8, 1511.9, 1218, 8 cm -1 NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.5Hz), 1.2-1.6 (6H, m), 1.6-1.9 (2H, m) ), 3.29 (4H, t, J = 3.6Hz), 3.44 (4H, t, J = 3.6Hz), 3.93 (2H, t, J = 6.5Hz), 6.87 (2H, d, J = 9.2Hz), 6.97 (2H, d, J = 9.2Hz), 7.19 (1H, d, J = 8.6Hz), 7.4-7.7 (3H, m), 8.10 (1H, d, J = 6.4Hz), 8.14 (1H, dd, J: 8.6 and 2.1Hz), 8.27 (1H, d, J = 2.1Hz): APCI MASS: m / z = 534 (M + + H)

Preparation 219: '1- [4- (4-Piperidinopiperidin-1-yl) benzoyl] -benzotriazole-3-oxide IR (KBr): 1758.8, 1602.6, 1186.0 cm -1 NMR (CDCl ): 1.35-1.8 (8H, m), 1.96 (2H, d, J = 13Hz), 2.45-2.7 (5H, m), 2.97 (2H, td, J = 12.8 and 2.6Hz), 4.04 (2H, d, J = 13Hz), 6.93 (2H, d, J = 9.2Hz), 7.35-7.6 (3H, m) 8.1-8.4 (3 H, m). Preparation 220: 1- 13- [4- (4-n-Hexyloxyphenyl) piperazin-1-yl] pyridazin-6-ylcarbonyl] benzotriazole-3-oxide IR (KBr): 1787.7, 1585.2, 1511.9 , 1240.0 cm -1

Preparation 221 73 1- [5- [4- (4-n-Hexyloxyphenyl) piperazin-1-yl] picolinoyl] -benzotriazole-3-oxide IR (KBr): 1766.5, 1575.6, 1511.9, 1232 3 cm -1 NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.5Hz), 1.2-1.6 (6H, m), 1.65-1.9 (2H, m), 3.27 (4H, t, J = 5.1Hz), 3.66 (4H, t, J = 5.1Hz), 3.93 (2H, t, J = 6.5Hz), 6, 88 (2H, d, J = 9.2Hz), 6.95 (2H, d, J = 9.2Hz), 7.25 (1H, dd, J = 7.6 and 2.9Hz), 7.35 -7.6 (3H, m), 8.09 (1H, d, J = 8.2Hz), 8.18 (1H, d, J = 8.9Hz), 8.52 (1H, d, J = 2.9Hz) APCI MASS: m / z = 501 (M + + H)

Preparation 222 1- [4- [4- (4-Cyclohexyl-phenyl) -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1770.3, 1602.6, 1515.8, 1232.3, 1186.0 cm -1 T NMR (CDCl 3, δ): 1.15-1.5 (6H, m), 1.65-2.0 (4H, m), 2.45 (1H, m), 3.33 ( 4H, t, J = 5.1Hz), 3.62 (4H, t, J = 5.1Hz), 6.92 (2H, d, J = 8.7Hz), 6.99 (2H, d, J 9.2Hz), 7.16 (2H, d, J = 8.7Hz), 7.35-7.65 (3H, m), 8.09 (1H, d, J = 8.2Hz), δ , 15 (2H, d, J = 9.2Hz)

Preparation 223 1- [4- [4- (4-n-Hexyl-phenyl) -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1768.4, 1602.6, 1515, 8, 1230, 4, 1184.1 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.5Hz), 1.2-1.45 (6H, m), 1.5-1 , 7: ·. (2H, m), 2.55 (2H, t, J = 7.6Hz), 3.2-3.4 (4H, m), 3.5-3.7 (4H, m), 6.91 (2H, d, J = 8.6Hz), 7.00 (2H, d, J = 9.1Hz), 7.13 (2H, d, J = 8.5Hz).

1 ': 7.35-7.6 (3H, m), 8.09 (1H, d, J = 8.2Hz), 8.15 (2H, d, J = 9.1Hz) ... Preparation 224 ; ' ": 1- [4- [4- (4-Phenyl-cyclohexyl) -piperazin-1-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1780.0, 1762.6, 1602.6, 1234.2, 1182.2 cm -1 NMR (CDCl 3, δ): 1.3-1.7 (4H, m), 1.95-2.15 (4H, m), 2.35-2.6 (2H, 1 m), 2.79 (4H, t, J = 5.0Hz), 3.49 (4H, t, J = 5.0Hz), 6.95 (2H, d, J = 9.0Hz), 7, 1-7.35 (5H, m), 7.35-7.6 (3H, m), 8.08 (1H, d, J = 7.1Hz), 8.12 (2H, d, J = 9) , 0Hz)

Preparation 225 74 1- [4- [4- [1- (4-n-Hexyloxyphenyl) piperidin-4-yl] piperazin-1-yl] benzoyl] benzotriazole-3-oxide IR (KBr): 1768.4, 1602 Δ, 1511.9, 1234.2 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.2-1.55 (6H, m), 6-1.9 (4H, m), 1.96 (2H, d, J = 11Hz), 2.44 (1H, m), 2.64 (2H, d, J = 1.1Hz), 2, 77 (4H, t, J = 5.0Hz), 3.48 (4H, t, J = 5.0Hz), 3.59 (2H, d, J = 11Hz), 3.91 (2H, t, J = 6.5Hz), 6.7-7.05 (6H, m), 7.35-7.6 (3H, m), 8.08 (1H, d, J = 6.9Hz), 8.12 (2H, d, J = 7.7Hz)

Preparation 226 1- [4- (4-Trans-n-Pentylcyclohexyl) benzoyl] -benzotriazole-3-oxide IR (KBr): 1799.3, 1778.0, 1608.3, 1228.4, 977.7 cm-1 NMR ( CDCl 3, δ): 0.91 (3H, t, J = 6.6Hz), 1.0-1.7 (13H, m), 1.93 (4H, d, J = 9.8Hz), 2, 62 (1H, t, J = 12Hz), 7.35-7.6 (5H, m), 8.09 (1H, d, J = 7.9Hz), 8.19 (2H, d, J = 8 , 4 Hz)

Preparation 227 1- (6- (8-Methoxy-octyloxy) -2-naphthoyl] -benzotriazole-3-oxide IR (KBr): 2931.3, 2856, 1, 1778, 0, 1623, 8 cm -1).

•: Preparation 228, 1- (E) - [3- [4- [4- (7-Fluoroheptyloxy) phenyl] phenyl] acryloyl] benzotriazole-3-oxide: - IR (KBr): 3070.1, 2935, 1, 2859.9, 1700.9, 1619.9, 1596.8 cm -1 NMR (CDCl 3, δ): 1.30-2.00 (10H, m), 4.02 (2H, t, J 6.4Hz), 4.45 (2H, dt, J = 47.5 and 6.2Hz), 6.70-8.65 (14H, m) .., Preparation 229: "; 1- (6- Heptylnaphthalene-2-carbonyl) -benzotriazole-3-oxide NMR (DMSO-d6, δ): 0.75-0.93 (3H, m), 1.10-1.45 (8H, m), 1.55-. 1.80 (2H, m), 2.68-2.90 (2H, m), 7.35-9.06 (10H, m) · APCI MASS: m / z = 388 (M + +1) )

Preparation 230 75 1- (E) - [3- [4- [4- (8-Methoxy-octyloxy) -phenyl] -phenyl] -acryloyl] -benzotriazole-3-oxide

Preparation 231 1- (E) - [3- [4- [4- (5-Hexenyloxy) phenyl] phenyl] acryloyl] -benzotriazole-3-oxide IR (KBr): 3072.0, 3033.5, 2939.0 , 2865.7, 1780.0, 1693.2, 1619.9, 1596.8 cm -1 NMR (DMSO-d6, δ): 1.43-1.66 (2H, m), 1.66-1 , 90 (2H, m), 2.02-2.23 (2H, m), 3.90-4.16 (2H, m), 4.90-5.13 (2H, m), 5.72 -6.00 (1H, m), 6.93-8.30 (14H, m) APCI MASS: m / z = 337 (methyl ester, M + +1).

Preparation 232 1- (E) - [3- [4- [4- (4-Methyl-pentyloxy) -phenyl] -phenyl] -acryloyl] -benzotriazole-3-oxide IR (KBr): 3072.0, 3033.5, 2952.5 , 2869.6, 1780.0, 1693.2, 1618.0, 1598.7 cm -1 NMR (DMSO-d6, δ): 0.90 (6H, d, J = 6.5Hz), 1.20 -1.40 (2H, m), 1.50-1.90 (3H, m), 3.90-4.10 (2H, m), 6.40-8.30 (14H, m) APCI- MASS: m / z = 442 (M + +1); 'r' Preparation 233 1- (E) - [3- [4- [4- (6-Fluorohexyloxy) -phenyl] -phenyl] - 'acryloyl] -benzotriazole-3-oxide v' IR (KBr): 3074.0, 3033.5, 2939.0, 2865.7, 1780.0, 1697.1, 1598.7 cm -1 NMR (DMSO-d 6, δ): 1.25-1.83 (6H, m), 4 04 (2H, t, J = 6.5Hz), 4.45 (2H, dt, J = 47.5 and 6.5Hz), 6.9-8.3 (14H, m) APCI MASS: m / z = 460 (M ++ 1)

Preparation 234 1- (E) - [3- [4- [4- (6-Methoxy-hexyloxy) -phenyl] -phenyl] -acryloyl] -benzotriazole-3-oxide NMR (DMSO-d6, δ): 1.30-1.65 (6H, m), 1.65-1.90 (2H, m), 3.22 (3H, s), 3.22-3.40 (2H, m), 4.02 (2H, t, J = 6.5Hz), 6.5-8.3 (14H, m) 76

Preparation 235 1- [4- [3- (4-n-Hexyloxyphenyl) pyrazol-5-yl] benzoyl] -benzotriazole-3-oxide IR (KBr): 2935, 1780, 1610, 1506, 1249, 1232, 1178, 1087 cm -1 NMR (CDCl 3, δ): 0.91 (3H, d, J = 6.4Hz), 1.2-1.6 (6H, m), 1.7-1.9 (2H, m), 3.98 (2H, t, J = 6.5Hz), 6.8-7.0 (3H, m), 7.4-7.6 (5H, m), 8.00 (2H, d, J = 8.4Hz), 8.10 (1H, d, J = 8.1Hz), 8.28 (1H, d, J = 8.4Hz) APCI MASS: m / z = 482 (M + H +)

Preparation 236 1- [4- [4- [4- (6-Methoxy-hexyloxy) -phenyl] -phenyl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 2935, 2858, 1774, 1600, 1490, 1257, 1211 cm -1. (CDCl 3, δ): 1.4-1.9 (8H, m), 3.35 (3H, s), 3.40 (2H, t, J = 6.3Hz), 4.02 (21H, t , J = 6.4Hz), 7.00 (2H, d, J = 8.7Hz), 7.4-7.8 (7H, m), 7.87 (2H, d, J = 8.4Hz) , 8.12 (1H, d, J = 8.2Hz), 8.36 (2H, d, J = 8.4Hz) APCI MASS: m / z = 522 (M + H +)

Preparation 237; ', 1- [4- [5- (4- (8-Methoxy-octyloxy) -phenyl] -1,3,4-thiadiazol-2'-yl) -benzoyl] -benzotriazole-3-oxide / 7 IR (KBr): 2929, 2854, 1776, 1602, 1469, 1255 cm -1: 7 NMR (CDCl 3, δ): 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3.33 (3H, s), 3.37 (2H, d, J = 6.4Hz), 4.03 (2H, d, J = 6.5Hz), 7.00 (2H, d, J = 8.9Hz): 7.4-7.6 (3H, m), 7.97 (2H, d, J = 8.9Hz), 8.12 (1H, d, J = 8.2Hz) , 8.23 (2H, d, J = 8.7Hz), 8.39 (2H, d, J = 8.7Hz) APCI MASS: m / z = 558 (M + H +) &lt; - &gt; 1,1- [4- (4-n-Butoxyphenyl) cinnamoyl] benzotriazole-3-oxide 7 IR (KBr): 2952, 2867, 1778, 1598, 1496, 1249, 1186 cm -1 NMR (CDCl 3, δ) : 0.99 (3H, t, J = 7.3Hz), 1.55 (2H, tq, J = 7.0 and ·; 7.3Hz), 1.78 (2H, tt, J = 7.0) and 6.4Hz), 4.02 (2H, t, J = 6.4Hz), 6.75.,: (1H, d, J = 16.0Hz), 7.00 (2H, d, J = 8.7Hz), 7.4-8.2 (9H, m) APCI MASS: m / z = 414 (M + H +)

Preparation 239 77 1- [4- [5- (4-Cyclohexyl-phenyl) -1,3,4-thiadiazol-2-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 2925, 2850, 1778, 1230 , 989 cm -1 NMR (CDCl 3, δ): 1.2-1.6 (5H, m), 1.7-2.0 (5H, m), 2.5-2.7 (1H, m) , 7.37 (2H, d, J = 8.3Hz), 7.4-7.6 (3H, m), 7.97 (2H, d, J = 8.3Hz), 8.13 (1H, d, J = 8.2Hz), 8.26 (2H, d, J = 8.6Hz), 8.42 (2H, d, J = 8.6Hz) APCI MASS: m / z = 482 (M +). H) +

Preparation 240 1- [4- [5- [4- (4-n-Propyloxyphenyl) phenyl] -1,3,4-oxadiazol-2-yl] benzoyl] benzotriazole-3-oxide IR (KBr): 1778, 1604 , 1488, 1249, 1232, 998 cm -1 NMR (CDCl 3, δ): 1.07 (3H, t, J = 7.4Hz), 1.85 (2H, tq, J = 6.5 and 7.4Hz ), 7.02 (2H, d, J = 8.8Hz), 7.4-7.7 (3H, m), 7.61 (2H, d, J = 8.8Hz), 7.75 (2H) , d, J = 8.5Hz), 8.14 (1H, d, J = 8.2Hz), 8.22 (2H, d, J = 8.5Hz), 8.40 (2H, d, J = 8.8Hz), 8.48 (2H, d, J = 8.8Hz) APCI MASS: m / z = 518 (M + H) +.

Preparation 241: 1- [4- (5-n-Nonyl-1,3,4-oxadiazol-2-yl) benzoyl] -benzotriazole-3-oxide IR (KBr): 2919, 2850, 1780, 1565, 1415 , 1251 cm -1: NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.7Hz), 1.2-1.6 (12H, m), 1.8-2.0 (2H) , m), 2.98 (2H, t, J = 7.7Hz), 7.4-7.6 (3H, m), 8.12 (1H, d, J = 9.0Hz), 8.28 (2H, d, J = 8.7Hz), 8.42 (2H, d, J = 8.7Hz) APCI MASS: m / z = 434 (M + H +)

Preparation 242; ; 1- [4- [3- (4-n-Hexyloxyphenyl) -1,2,4-oxadiazol-5-yl] -,, benzoyl] -benzotriazole-3-oxide IR (KBr): 2946, 2869, 1780, 1251, 1230, 1001 cm -1 1 H NMR (CDCl 3, δ): 0.92 (3H, t, J = 6.8Hz), 1.3-1.6 (6H, m), 1.8-1.9 (2H, ·;> m), 4.04 (2H, t, J = 6.5Hz), 7.03 (2H, d, J = 8.9Hz), 7.4-7.6 (3H, m) ), 8.0-8.2 (3H, m), 8.46 (4H, s) APCI MASS: m / z = 484 (M + H +)

Preparation 243 78 1- [4- [5- (4-n-Octyloxyphenyl) -1,3,4-thiadiazol-2-yl] benzoyl] benzotriazole-3-oxide IR (KBr): 2925, 2856, 1774; 1602, 1259, 1232, 989 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.7Hz), 1.1-1.6 (10H, m), 1.7-1 , 9 (2H, m), 4.04 (2H, t, J = 6.5Hz), 7.01 (2H, d, J = 8.9Hz), 7.4-7.6 (3H, m) , 7.97 (2H, d, J = 8.8Hz), 8.12 (1H, d, J = 8.2Hz), 8.24 (2H, d, J = 8.6Hz), 8.40 ( 2H, d, J = 8.6Hz) APCI MASS: m / z = 528 (M + H +)

Preparation 244 1- [4- [5- (4-Trans-n-Pentylcyclohexyl) -1,3,4-thiadiazol-2-yl] benzoyl] -benzotriazole-3-oxide IR (KBr): 2952, 2919, 2848; 1785, 1444, 1226, 991 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.9Hz), 1.0-1.7 (13H, m), 1.94 (2H, d) , J = 12.0Hz), 2.27 (2H, d, J = 12.0Hz), 3.19 (1H, tt, J = 12.0 and 3.6Hz), 7.4-7.6 ( 3H, m), 8.12 (1H, d, J = 8.6Hz), 8.19 (2H, d, J = 8.6Hz), 8.38 (2H, d, J = 8.6Hz) APCI MASS: m / z = 476 (M + H +)

Preparation 245 ', 1- [4- [3- (4-n-Pentyloxy-phenyl) -isoxazol-5-yl] -benzoyl] -benzotriazole-3-oxide: IR (KBr) -2948, 2867, 1776; 1610, 1436, 1253, 1002 cm -1 NMR (CDCl 3, δ): 0.95 (3H, t, J = 7.1 Hz), 1.2-1.6 (4H, m), 7-1.9 (2H, m), 4.02 (2H, t, J = 6.5Hz), 7.0-7.1 (3H, m), 7.4-7.6 (3H, m) ), 7.81 (2H, d, J = 8.8Hz), 8.06 (2H, d, J = 8.6Hz), 8.12 (1H, d, J = 8.0Hz), 8.39 (2H, d, J = 8.6Hz) APCI MASS: m / z = 469 (M + H +) /; Preparation 246 "" 1- [4- [5- [4- (8-Methoxyoctyloxy) phenyl] " -1,3,4-oxadiazole-2 '> 1'; yl] benzoyl] benzotriazole-3-oxide IR (KBr): 2923, 2854, 1787, 1608, 1494, 1255, 1228, 993 cm -1 NMR (CDCl 3, δ): 1.2-1.6 (10H, m ), 1.7-1.9 (2H, m), 3.34 (3H, s), 3.38 (2H, t, J = 6.4Hz), 4.05 (2H, t, J) = 6.5Hz), 7.04 (2H, d, J = 8.8Hz), 7.4-7.6 (3H, s), 8.1-8.2 (3H, s), 8.36 (2H, d, J = 8.7Hz), 8.45 (2H, d, J = 8.7Hz) 79 APCI MASS: m / z = 542 (M + H +)

Preparation 247 1- [4- [4- (6-Phenyl-pyridazin-3-yloxy] -phenyl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 1783, 1604, 1423, 1284, 985 cm -1 NMR (CDCl δ): 7.2-8.2 (15H, m), 8.12 (2H, d, J = 8.3Hz), 8.36 (2H, d, J = 8.4Hz) APCI MASS: m / z = 486 (M ++ 1)

Preparation 248 1- [4- [5- (4-n-Octyloxy-phenyl) -1,3,4-oxadiazol-2-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 2925, 2854, 1780, 1610 , 1496, 1257, 1228, 1180 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-2.0 (12H, m), 4.05 ( 2H, t, J = 6.5Hz), 7.05 (2H, d, J = 8.7Hz), 7.4-7.6 (3H, m), 8.0-8.2 (3H, m) ), 8.37 (2H, d, J = 8.6Hz), 8.45 (2H, d, J = 8.6Hz) APCI MASS: m / z = 512 (M + H +)

Preparation 249: 1- [4- [2- (4-n-Hexyloxyphenyl) pyrimidin-6-yl] benzoyl] -benzotriazole-3-oxide IR (KBr): 2948, 2861, 1780, 1552, 1413, 1378 1 H NMR (CDCl 3, δ): 0.92 (3H, t, J = 6.8Hz), 1.2-1.6 (6H, m), 1.8-2.0 (2H, m), 4.06 (2H, t, J = 6.5Hz), 7.04 (2H, d, J = 9.0Hz), 7.4-7.6 (3H, m), "7, 64 (1H, d, J = 5.2Hz), 8.13 (1H, d, J = 8.2Hz), 8.44 (4H, s), 8.55: (2H, d, J = 9, 0Hz), 8.90 (1H, d, J = 5.2Hz) APCI MASS: m / z = 494 (M + H +)

Preparation 250. '', 1- [4- [4- [8- (2-Ethoxyethoxy) octyloxy] phenyl] benzoyl] - ', benzotriazole-3-oxide IR (KBr): 2933, 2861, 1778, 1598, 1247, 1186, 977 cm -1 11 'NMR (CDCl 3, δ): 1.22 (3H, t, J = 7.0Hz), 1.3-2.0 (14H, m), 3.4-3 , 6 (6H, m), 4.02 (2H, t, J = 6.5Hz), 7.02 (2H, d, J = 8.8Hz), 7.4-7.6 (3H, m) , 7.62 (2H, d, J = 8.8Hz), 7.78 (2H, d, J = 8.6Hz), 8.10 (1H, d, J = 8.9Hz), 8.31 ( 2H, d, J = 8.6Hz) 80 APCI MASS: m / z = 532 (M + H +)

Preparation 251 1- [4- [4- [7- (Piperidin-1-ylcarbonyl) heptyloxy] phenyl] benzoyl] benzotriazole-3-oxide IR (KBr): 2935, 2856, 1774, 1631, 1598, 1255, 1191 cm -1 NMR (CDCl 3, δ): 1.3-2.0 (16H, m), 2.37 (2H, t, J = 7.6Hz), 3.48 (4H, s), 4.02 (2H, t, J = 6.4Hz), 7.02 (2H, d, J = 8.6Hz), 7.4-7.6 (3H, m), 7.63 (2H, d, J = 8.6Hz), 7.78 (2H, d, J = 8.3Hz), 8.11 (1H, d, J = 8.3Hz), 8.31 (2H, d, J = 8.3Hz) APCI MASS: m / z = 541 (M + H +)

Preparation 252 1- [6- [4- (4-η-Heptyloxyphenyl) piperazin-1-yl] nicotinoyl] -benzotriazole-3-oxide IR (KBr): 2929, 2856, 1762, 1604, 1510, 1240 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.7Hz), 1.2-1.9 (10H, m), 3.20 (4H, t, J = 5.0Hz), 3.8-4.0 (6H, m), 6.75 (1H, d, J = 9.5Hz), 6.86 (2H, d, J = 9.3Hz), 6.95 (2H, d) , J = 9.3Hz), 7.3-7.6 (3H, m), 8.10 (1H, d, J = 8.2Hz), 8.19 (1H, dd, J = 9.2 and 2.3Hz), 9.05 (1Ή, d, J = 2.3Hz) APCI MASS: m / z = 515 (M + H +),; 1, Preparation 253 ',' 1- [6- [4- [4- (8-Methoxy-octyloxy) -phenyl] -piperazin-1-yl] -: ''; nicotinoyl] benzotriazole-3-oxide IR (KBr): 2929, 2854, 1766, 1602, 1510, 1419, 1234 cm -1 NMR (CDCl 3, δ): 1.3-1.9 (12H, m), 3 2-3.3 (4H, m), 3.33 (3H, s), 3.36 (2H, t, J = 6.4Hz), 3.92 (2H, t, J = 6.5Hz), 4.0-4.2 (4H, m), 6.75 (1H, d, J = 9.1Hz), 6.87 (2H, d, J = 8.9Hz), 7.0-7, 2 (2H, m), 7.4-7.6: (3H, m), 8.09 (1H, d, J = 8.1Hz), 8.20 (1H, dd, J = 9.1 and 2.3Hz), 9.05 (1H, d, J = 2.3Hz). APCI MASS: m / z = 559 (M + H +),; Preparation 254 CC 1- [4- [5- [4- (4-n-Propyloxyphenyl) phenyl] -1,3,4-thiadiazole-2 - yl] benzoyl] benzotriazole-3-oxide IR (KBr): 1774, 1600, 1234, 985 cm -1 81 NMR (CDCl 3, δ): 1.07 (3H, t, J = 7.3 Hz), 1, 85 (2H, tq, J = 6.5 and 7.3Hz), 3.99 (2H, t, J = 6.5Hz), 7.01 (2H, d, J = 8.7Hz), 7.4 -7.7 (5H, m), 7.72 (2H, d, J = 8.7Hz), 8.1-8.2 (2H, m), 8.28 (2H, d, J = 8, 6Hz), 8.44 (2H, d, J = 8.6Hz) APCI MASS: m / z = 534 (M + H) +.

The following compounds (Preparations 255-256) were obtained in the same manner as Preparation 32.

Preparation 255 6-Heptylnaphthalene-2-carboxylic acid NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.6Hz), 1.15-1.53 (8H, m), 1.58-1, 88 (2H, m), 2.80 (2H, t, J = 7.6Hz), 7.42 (1H, dd, J = 1.7 and 8.4Hz), 7.67 (1H, s), 7.84 (1H, d, J = 8.6Hz), 7.90 (1H, d, J = 8.4Hz), 8.09 (1H, dd, J = 1.7 and 8.6Hz), δ , 68 (1 H, s) APCI MASS: m / z = 271 (M + +1), 285 (methyl ester-1).

Preparation 256 3- (E) - [4- [4- (7-Fluoroheptyloxy) phenyl] phenyl] acrylic acid IR (KBr): 3037.3, 2935.1, 2861.8, 1679.7, 1633.4, 1600 6 cm -1 NMR (DMSO-d 6, δ): 1.30-1.85 (10H, m), 4.01 (2H, t, J = 6.4Hz), 4.44 (2H, dt, J = 47.6 and 6.1Hz), 6.54 (1H, d, J = 15.9Hz), 7.02 (2H, d, J = 8.7Hz), 7.53-7.80 (7H , m) 'Preparation 257. To a solution of 4-methylpentanol (3.0 ml) in pyridine (20' 11 ml) was added alternately p-toluenesulfonyl chloride: (4.6 g) and 4-N, N-dimethylaminopyridine (1.5 g) at ambient temperature. After stirring at ambient temperature, the reaction mixture was dissolved in a mixture of ethyl acetate (100 mL) and water (100 mL). The separated organic layer was washed alternately with hydrochloric acid (1N), water, aqueous sodium hydrogen carbonate and brine, and dried over magnesium sulfate.

Evaporation gave 1-p-toluenesulfonyl-oxy-4 '' methylpentane (5.30 g).

NMR (CDCl 3, δ): 0.83 (6H, d, J = 6.6Hz), 1.48 (1H, sept, J = 6.6Hz), g '; 1.50-1.70 (2H, m), 2.45 (3H, s), 4.00 (2H, t, J = 6.6Hz), 7.34 (2H, d, J = 8, 1Hz), 7.79 (2H, d, J = 8.1Hz) APCI MASS: m / z. = 257 (M + + 1)

Preparation 258 82

To a solution of 4-bromo-4'-n-butyloxybiphenyl (3.05 g) in tetrahydrofuran (60 ml) was added 1.55 M n-butyl lithium in n-hexane (7.74 ml) at -60 ° C. For a 10 minute period. The solution was stirred at -30 ° C for 1.5 hours and cooled to -60 ° C. Triisopropylborate (3.46 mL) was added to the solution over a 5 minute period and the mixture was stirred for 1.5 hours without cooling. To the solution was added 1N hydrochloric acid (20 mL), and the solution was stirred for 30 minutes and extracted with ethyl acetate. The organic layer was separated and washed with water, brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with n-hexane. The solid was collected by filtration and dried under reduced pressure to give 4- (4-n-butyloxyphenyl) phenyl boronic acid (2.31 g).

IR (KBr): 3398, 2956, 2919, 2871, 1604, 1531, 1392, 1257 cm-1 NMR (DMSO-d6, δ): 0.94 (3H, t, J = 7.3Hz), 1.4-1 , Δ (4H, m), 4.01 (2H, t, J = 6, 3Hz), 7.01 (214, d, J = 8.7Hz), 7.58 (2H, d, J = 7, 9Hz), 7.62 (2H, d, J = 8.7Hz), 7.84 (2H, d, J = 7.9Hz), 8.03 (2H, s)

The following compounds (Preparations 259-260) were obtained in the same manner as Preparation 258.

Preparation 259 1; ·, 4- [4- (6-Methoxyhexyloxy) phenyl] phenylboronic acid IR (KBr): 3448, 3392, 2937, 2861, 1606, 1529, 1346, 1288 cm -1 NMR (DMSO-d 6, δ): 1.3 -1.8 (8H, m), 3.21 (3H, s), 3.31 (2H, t, J = 6.3Hz), 3.99 (2H, t, J = 6.4Hz), 7 , 00 (2H, d, J = 8.7Hz), 7.5-7.7 (4H, im), 7.84 (2H, d, J = 8.1Hz), 8.03 (2H, s) V: AP.CI.MASS: m / z · = 329 (M + H +);, Preparation 260 '-4- [4- (5-Methoxy-pentyloxy) -phenyl] -phenylboronic acid IR (KBr): 3473, 3369, 3330 , 2935, 2863, 1604, 1531, 1338, 1251 cm -1, 1 H NMR (DMSO-d 6, δ): 1.4-1.8 (6H, m), 3.22 (3H, s), 3 3-3.4 (2H, m), 3.99 (2H,, t, J = 6.4Hz), 7.00 (2H, d, J = 8.7Hz), 7.58 (2H, d, J = 8.0Hz), 7.61 (2H, d, J = 8.7Hz), 7.84 (2H, d, J = 8.0Hz), 8.04 (2H, s) APCI MASS: m / z = 315 (M + H +) 83

Preparation 261

To a suspension of 4-methoxycarbonylphenylboronic acid (648 mg) and 4-iodo-1-heptylpyrazole (876 mg) and Pd (PF 3) 4 (173 mg) in 1,2-dimethoxyethane (10 mL) were added 2M aqueous Na 2 CO 3 (3.6 mL). The reaction mixture was stirred at 80 ° C for 2 hours under N 2 and poured into ice water and extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO 4. The solvent was removed under pressure. The residue was subjected to column chromatography on silica gel 60 (Merk) and eluted with n-hexane / ethyl acetate (80:20). The fractions containing the target compound were combined and evaporated under reduced pressure to give 1-heptyl-4- (4-methoxycarbonylphenyl) pyrazole (0.20 g).

IR (KBr pellet): 2952, 2920, 2848, 1712, 1610, 1288, 1114, 769 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.7Hz), 1 , 1-1.4 (8H, m), 1.7-1.9 (2H, m), 3.85 (3H, s), 4.11 (2H, t, J = 7.0Hz), 7 , 72 (2H, d, J = 8.5Hz), 7.93 (2H, d, J = 8.5Hz), 7.99 (1H, s), 8.34 (1H, s) APCI MASS: m / z = 301 (M + H +)

The following compounds (Preparations 262-268) were obtained in the same manner as Preparation 261.

; ',, Preparation 262! , Ethyl 4- [4- (4-n-butyloxyphenyl) phenyl] benzoate 1 H IR (KBr): 2958, 2935, 2871, 1714, 1602, 1396, 1280, 1108 cm -1 NMR (CDCl 3, δ ): 0.99 (3H, t, J = 7.3Hz), 1.4-2.0 (7H, m), 4.02 (2H, t, and 1 J = 6.4Hz), 4.40 (2H, q, J = 7.1Hz), 6.98 (2H, d, J = 6.8Hz), 7.56 (2H, d, J = 6.8Hz), 7.66 (4H, s) , 7.68 (2H, d, J = 8.4Hz), 8.12 (2H, d, J = 8.4Hz) APCI MASS: m / z = 375 (M + H) +,, Preparation 263 '', Methyl 6- (4-heptyloxyphenyl) nicotinate IR (KBr): 2954, 2859, 1724, 1597, 1288, 1251, 1116, 783 cm -1. 1 H NMR (CDCl 3, δ): 0.90 ( 3H, t, J = 6.6Hz), 1.2-1.5 (8H, m), 1.7-1.9 (2H, m), 3.96 (3H, s), 4.03 ( 2H, t, J = 6.5Hz), 7.00 (2H, d, J = 8.8Hz), 7.75 (1H, d, J = 8.4Hz), 8.02 (1H, d, J) = 8.8Hz), 8.30 (1H, dd, J = 8.4 and 2.2Hz), 9.23 (1H, d, J = 2.2Hz) APCI MASS: m / z = 328 (M + H +)

Preparation 264 84

Methyl β- [4- (4-n-butyloxyphenyl) phenyl] nicotinate IR (KBr): 2956, 2933, 2871, 1724, 1598, 1282, 1118 cm -1 NMR (CDCl 3, δ): 1.00 (3H) , t, J = 7.3Hz), 1.4-1.9 (4H, m), 3.98 (3H, s), 4.02 (2H, t, J = 6.4Hz), 7.00 (2H, d, J = 8.8Hz), 7.59 (2H, d, J = 8.8Hz), 7.70 (2H, d, J = 8.5Hz), 7.86 (1H, d, J = 8.8Hz), 8.13 (2H, d, J = 8.5Hz), 8.37 (1H, dd, J = 8.8 and 1.6Hz), 9.30 (1H, d, J = 1.6Hz) APCI MASS: m / z = 362 (M + H +)

Preparation 265

Methyl 5- [4- (4-n-butyloxyphenyl) phenyl] furan-2-carboxylate IR (KBr): 2958, 2933, 2873, 1716, 1483, 1303, 1139 cm-1 NMR (CDCl3, δ) 0.99 (3H, t, J = 7.3Hz), 1.5-1.9 (4H, m), 3.93 (3H, s), 4.01 (2H, t, J = 6, 4Hz), 6.75 (1H, d, J = 3.6Hz), 6.98 (2H, d, J = 8.7Hz), 7.26 (1H, d, J = 3.6Hz), 7, 56 (2H, d, J = 8.4Hz), 7.61 (2H, d, J = 8.7Hz), 7.83 (2H, d, J = 8.4Hz) APCI MASS: m / z = 351 (M + H) +: 1, Preparation 266 1 · 1 Ethyl 4- [4- [4- (6-methoxyhexyloxy) phenyl] phenyl] benzoate: 1,1 IR (KBr): 2937, 2863 , 1712, 1602, 1396, 1278, 1108 cm -1 1 H NMR (CDCl 3, δ): 1.4-2.0 (11H, m), 3.34 (3H, s), 3.39 ( 2H, t, 1H, J = 6.4Hz), 4.01 (2H, t, J = 6.4Hz), 4.41 (2H, q, J = 7.1Hz), 6.98 (2H) , d, J = 8.7Hz, 7.56 (2H, d, J = 8.7Hz), 7.6-7.8 (6H, m), 8.12 (2H, d, J). = 8.4 Hz) APCI MASS: m / z = 433 (M + H +) 4 -; Preparation 267 · 1 '4 - [4- [4- (5-Methoxy-pentyloxy) -phenyl] -phenyl] -benzoic acid 1' IR ( KBr): 2939, 2859, 1679, 1587, 1396, 1321, 1292, 1126 cm -1 NMR (DMSO-d 6, δ): 1.3-1.8 (6H, m), 3.21 (3H, s) ) , 3.2-3.4 (2H, m), 4.01 (2H, t, J = 6.5 Hz), 7.04 (2H, d, J = 8.6 Hz), 7.66 (2H , d, J = 8.6Hz, 7.7-7.9 (6H, m), 8.03 (2H, d, j = 8.2Hz) APCI MASS: m / z = 391 (M + H +) )

Preparation 268 85

Methyl 4- [4- [4- (5-methoxypentyloxy) phenyl] phenyl] phenylacetate IR (KBr): 2937, 2863, 1739, 1604, 1492, 1255 cm -1 NMR (CDCl 3, δ): 1, 5-2.0 (6H, m), 3.34 (3H, s), 3.42 (2H, t, J = 6.3Hz), 3.68 (2H, s), 3.72 (3H, s), 4.02 (2H, t, J = 6.4Hz), 6.97 (2H, d, J = 8.7Hz), 7.36 (2H, d, J = 8.2Hz), 7, 5-7.7 (8H, m) APCI MASS: m / z = 419 (M + H +)

Preparation 269

A solution of 3- [2- (4-hexyl-phenylamino) -ethyl] -2-oxo-oxazolidine hydrochloride (2.131 g) in 25% hydrobromic acid in acetic acid (13.04 ml) was stirred for 96 hours at ambient temperature. The reaction mixture was made powdered with diisopropyl ether. The precipitate was collected by filtration and added to ethanol (15 mL). The solution was refluxed for 5 hours and powdered with diisopropyl ether. The precipitate was collected by filtration to give 1- (4-n-hexylphenyl) piperazine dihydrobromide (2.413 g) · IR (KBr): 2921.6, 2711.4, 2485.8, 1452.1, 1012.4 cm -1 (DMSO-d6, δ): 0.85 (3H, t, J = 6.6Hz), 1.1-1.4 (6H, m), 1.4-1.6 (2H, m), 2 , 49 (2H, t, J = 8.4Hz), 3.1-3.4 (8H, m), 6.54 (2H, s), 6.90 (2H, d, J = 8.7Hz) , 7.08 (2H, d, J = 8.7Hz), 8.78 (1H, s) APCI MASS: m / z = 247 (M + + H) ': 1' The following compounds (Preparations 270- 274) was obtained in the same manner as Preparation 269.

'.' 'Preparation 270:', 4- [4- (4-n-Hexylphenyl) piperazin-1-yl] benzoic acid dihydrobromide ':' 'IR (KBr): 2956, 3, 1691.3, 1664.3, 1602, 6 1232.3 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.5Hz), 1.2-1.4 (10H, m), 1.4-1, Δ (2H, m), 2.51 (2H, t, J = 7.4Hz), 3.2-3.6 (8H, m), 7.0-7.2 (6H, m), δ, 81 (2H, d, J = 8.8Hz) APCI MASS: m / z = 367 (M + + H)

Preparation 271 86 1- (4-Cyclohexylphenyl) piperazine dihydrobromide IR (KBr): 2927.4, 1510.0, 1452.1 cm -1 NMR (DMSO-d 6, δ): 1.1-1.5 (6H, m ), 1.6-1.9 (4H, m), 2.41 (1H, m), 3.1-3.4 (8H, m), 6.91 (2H, d, J = 8.7Hz) ), 7.11 (2H, d, J = 8.7Hz), 8.78 (1H, s) APCI MASS: m / z = 245 (M + + H)

Preparation 272 4- [4- (4-Cyclohexylphenyl) piperazin-1-yl] benzoic acid dihydrobromide IR (KBr): 1668.1, 1602.6, 1230.4, 1189.9 cm -1 APCI MASS: m / z = 365 (M ++ H)

Preparation 273 3-Fluoro-4- [4- (4-hydroxyphenyl) piperazin-1-yl] benzoic acid dihydrobromide IR (KBr): 1708.6, 1610.3 cm -1 NMR (DMSO-d 6, δ): 3 , 2 to 3.6 (8H, m), 6.81 (2H, d, J = 8.6Hz), 7.0-7.4 (3H, m), 7.4-7.8 (2H, m): APCI MASS: m / z = 317 (M + + H); 1,1 ', Preparation 274 4- [4- (4-Hydroxyphenyl) piperazin-1-yl] benzoic acid dihydrobromide; "IR (KBr): 1670.1, 1604.5, 1226.5, 775.2 cm -1 NMR (DMSO-d6, δ): 3.0-3.2 (4H, m), 3.3- 3.5 (4H, m), 6.68 (2H, d, J = 8.8Hz), 6.85 (2H, d, J = 8.8Hz), 7.02 (2H, d, J = 8) , 8Hz), 7.79 (2H, d, J = 8.8Hz), 8.86 (1H, s), 12.29 (1H, s), APCI MASS: m / z = 299 (M + H +). ) '; Preparation 275

A mixture of 4-n-hexyloxyaniline (10 g), ethyl acrylate (56.1 mL), glacial acetic acid (19.25 mL), and copper chloride (1.02 g) 1; was heated at reflux under nitrogen for 26 hours. A solution of the cold product in ether was shaken with water and then with ammonia solution. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate 87 was separated by filtration and the filtrate was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with hexane-ethyl acetate (9: 1). The fractions containing the target compound were combined and evaporated under reduced pressure to give ethyl 3- [N- (2-ethoxycarbonyl-ethyl) -N- (4-hexyloxyphenyl) amino] propionate (15.756 g).

IR (neat): 1733.7, 1513.8, 1241.9, 1182.2 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.2-1 , 55 (6H, m), 1.24 (6H, t, J = 7.1Hz), 1.65-1.85 (2H, m), 2.51 (4H, t, J = 7.2Hz) , 3.53 (4H, t, J = 7.2Hz), 3.89 (2H, t, J = 6.5Hz), 4.12 (4H, q, J = 7.1Hz), 6.72 ( 2H, d, J = 9.3Hz), 6.83 (2H, d, J = 9.3Hz) APCI MASS: m / z = 394 (M + + H)

Preparation 276

A suspension of methyl 4-formylbenzoate (4.92 g), hydroxylamine hydrochloride (5.21 g) and sodium acetate (6.15 g) in ethanol (50 ml) was refluxed for 2 hours. The mixture was poured into water and extracted with ethyl acetate, and the separated organic layer was washed with brine and dried over magnesium sulfate. The solvents were removed under reduced pressure to give 4-methoxycarbonylbenzaldehyde oxime (5.28 g).

IR (KBr): 3291, 1727, 1438, 1284, 1112 cm -1: NMR (CDCl 3, δ): 3.93 (3H, s), 7.65 (2H, d, J = 8.3Hz), δ , 10 (2H, d, V: J = 8.3Hz), 8.18 (1H, s), 8.27 (1H, s) APCI MASS: m / z = 180

The following compound was obtained in the same manner as Preparation 276.

:; '; Preparation 277, "N-Hydroxy-4-n-hexyloxybenzamidine: IR (KBr): 3446, 3349, 2937, 2865, 1650, 1610, 1519, 1392,". ('12 53 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.4Hz), 1.2-1.8 (8H, m), 3.97 (2H, t, J = 6.5Hz), 5.70 (2H, s), 6.90 (2H, d, J = 8.4Hz), 7.58 (2H, d, J * 8.4Hz), 9.43 (1H, s) APCI MASS: m / z = 237 (M + H) +

Preparation 278 88

To a solution of 4-methoxycarbonylbenzaldehyde oxime (896 mg) in N, N-dimethylformamide (10 ml) was added 4N-hydrochloric acid in 1,4-dioxane (1.38 ml) and oxone R (1.69 g). The suspension was stirred at ambient temperature for 16 hours and poured into ice water. The target compound was extracted with ethyl acetate, and the organic layer was washed with brine, dried over magnesium sulfate. The solvents were removed under reduced pressure to give 4-methoxycarbonyl-benzaldehyde oxime chloride (1.05 g).

IR (KBr): 3390, 1710, 1436, 1405, 1284, 1232, 1116, 1016 cm -1 NMR (CDCl 3, δ): 3.95 (3H, s), 8.93 (2H, d, J = 8 , 3Hz), 8.10 (2H, d, J = 8.7Hz), 8.39 (1H, s) APCI MASS: m / z = 176 (M-H + -HCl).

Preparation 279

A solution of ethyl 4-oxo-1- (4-n-hexyloxyphenyl) -piperidine-3-carboxylate (1.437 g) in 20% hydrochloric acid (7.2 ml) was refluxed for 2 hours, cooled, basified with 60% aqueous sodium hydroxide , and extracted with ethyl acetate. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was evaporated; under reduced pressure to give 1- (4-n-hexyloxyphenyl) -4-; piperidonia (0.959 g).

| V; IR (neat): 2931.3, 1716.3, 1511.9, 1243, 9, 825, 4 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz), 1.2-1.6 (6H, m), 1.65-1.85; ι (2H, m), 2.57 (4H, t, J = 6.1 Hz), 3.46 (4H, t) , J = 6.1Hz), 3.92 (2H, t, "J = 6.5Hz), 6.85 (2H, d, J = 9.3Hz), 6.95 (2H, d, J = 9.3 Hz) v 'APCI MASS: m / z = 276 (M + + H); g, Preparation 280' / A solution of 4- [4- (7-bromoheptyloxy) phenyl] bromobenzene; 25 g) in a solution of tetra-n-butylammonium fluoride (tetrahydrofuran solution, 1M, 2.9 ml) was heated to 50 ° C for 2 hours. After cooling to ambient temperature, the solution was dissolved in a mixture of ethyl acetate (20 mL) and water (20 mL). The separated organic layer was washed with water, brine and dried over magnesium sulfate. Evaporation gave a residue which was chromatographed on silica gel (30 mL) eluting with a mixture of n-hexane and ethyl acetate (100: 0-97: 3, 89 V / V). The fractions containing the target compound were collected and evaporated to a residue which was triturated with n-hexane to give 4- [4- (7-fluoroheptyloxy) phenyl] bromobenzene (104 mg).

IR (KBr): 2937.1, 2859.9, 1606.4 cm -1 NMR (CDCl 3, δ): 1.20-1.90 (10H, m), 3.99 (2H, t, J = 6 , 4Hz), 4.45 (2H, dt, J = 47.3 and 6.1Hz), 6.95 (2H, d, J = 6.7Hz), 7.40 (2H, d, J = 6, 7Hz), 7.47 (2H, d, J = 6.7Hz), 7.52 (2H, d, J = 6.7Hz)

The following compound was obtained in the same manner as Preparation 280.

Preparation 281 4- [4- (6-Fluorohexyloxy) phenyl] bromobenzene NMR (CDCl 3, δ): 1.40-1.95 (8H, m), 4.01 (2H, t, J = 6.4Hz), 4.47 (2H, dt, J = 47.5 and 6.0Hz), 6.95 (2H, d, J = 8.6Hz), 7.35-7.59 (6H, m)

Preparation 282

A solution of 4- [4- (8-bromooctyloxy) phenyl] bromobenzene (3.7 g) in a mixture of sodium methoxide (4.9M in methanol, 17 ml), N, N-dimethylformamide (20 ml) and tetrahydrofuran ( 8 ml) was heated to 80 ° C for 3 hours. The reaction mixture was dissolved in a mixture of ethyl acetate (200 mL) and water (100 mL). The separated organic layer was washed alternately with water, saturated brine, dried over magnesium sulfate. Evaporation gave a residue which was subjected to column chromatography (silica gel, 100 mL) eluting with i, n-hexane to give 4- [4- (8-methoxyoctyloxy) phenyl] bromobenzene (2.73 g).

: I; IR (KBr): 2935.1, 2858.0, 1604.5 cm -1, 1 H NMR (CDCl 3, δ): 1.25-1.70 (10H, m), 1.70-1.95 ( 2H, m), 3.33 (3H, s), 3.37 (2H, t, J = 6.5Hz), 3.99 (2H, t, J = 6.5Hz), 6.95 (2H, d, J = 8.8Hz), 7.35-7.66 (6H, m) APCI MASS: m / z = 391 (M +) h · - 'The following compounds (Preparations 283-284) were obtained in a similar manner,' '1 as preparation 282.

Preparation 283 ", 4-t4- (6-Methoxyhexyloxy) phenyl] bromobenzene. NMR (CDCl3, δ): 1.50-1.70 (6H, m), 1.70-1.95 (2H, m) , 3.34 (3H, s), 3.40 (2H, t, J = 6.2Hz), 3.99 (2H, t, J = 6.5Hz), 6.95 (2H, d, J = 8.7Hz), 7.30-7.60 (6H, m) 90 APCI MASS: m / z = 365 (M + + 2)

Preparation 284 4- [4- (7-Methoxyheptyloxy) phenyl] bromobenzene IR (KBr): 2935.1, 2854.1, 1604.5 cm -1 NMR (CDCl 3, δ): 1.25-1.70 (8H, m ), 1.70.1.95 (2H, m), 3.33 (3H, s), 3.37 (2H, t, J = 6.4Hz), 3.98 (2H, t, J = 6) , 5Hz), 6.95 (2H, d, J = 8.8Hz), 7.35-7.56 (6H, m) APCI MASS: m / z = 379 (M + + 2).

Preparation 285 N- (4-Octylphenyl) -N1-aminourea, formamidine acetate (12.76 g) and N-carbazoyl-4-octylaniline (6.458 g) in N, N-dimethylformamide (19.4 mL) were stirred at 150 ° C. in 6 hours. The reaction mixture was made powdered with water. The precipitate was collected by filtration and washed with water to give 4- (4-octylphenyl) -2,3-dihydro-4H-1,2,4-triazol-3-one (4.27 g).

IR (KBr): 3214.8, 3085.5, 1704.8 cm -1 NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.7Hz), 1.2-1.5 (10H) , m), 1.5-1.8 (2H, m), 2.64 (2H, t, J = 7.9Hz), 7.29 (2H, d, J = 8.5Hz), 7.43 (2H, d, J = 8.5Hz), 7.67 (1H, d, J = 1.3Hz), 10.31 (1H, s): APCI MASS: m / z = 274 (M + H +). The following compound (Preparation 286) was obtained in a similar manner to Preparation 285.

Preparation 286 4- [4- (4-tert-Butoxycarbonyl-piperazin-1-yl) -phenyl] -2,3-: dihydro-4H-1,2,4-triazol-3-one IR (KBr): 3200, 1699; 0.918.0 cm -1 NMR (CDCl 3, δ): 1.49 (9H, s), 3.17 (4H, t, J = 4.9Hz), 3.60 (4H, t, '··· J = 4.9Hz), 7.00 (2H, d, J = 9.0Hz), 7.40 (2H, d, J = 9.0Hz), 7.63 (1H, s), 10.4 (1 H, s) APCI MASS: m / z = 346 (M + H +) ': Preparation 287

A mixture of methyl 6- (1-heptynyl) naphthalene-2-carboxylate (4.51 g) and platinum oxide (0.4 g) in tetrahydrofuran was stirred at 3.5 atm of hydrogen for 5 hours. The catalyst was filtered off and the filtrate was evaporated to give methyl 6-heptylnaphthalene-2-carboxylate (4.40 g).

NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.6Hz), 1.16-1.50 (8H, m), 1.50-1.80 (2H, m), 2, 78 (2H, t, J = 7.6Hz), 3.97 (3H, s), 7.39 (1H, dd, J = 17 and 8.4Hz), 7.64 (1H, s), 7, 79 (1H, d, J = 8.6Hz), 7.86 (1H, d, J = 8.4Hz), 8.02 (1H, dd, J = 1.7 and 8.6Hz), 8.57 (1H , s) APCI MASS: m / z = 285 (M + +1).

The following compound (Preparation 288) was obtained in the same manner as Preparation 287.

Preparation 288

Methyl 6-hexylnaphthalene-2-carboxylate NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.8Hz), 1.17-1.53 (6H, m), 1.60-1. 82 (2H, m), 2.79 (2H, t, J = 7.7Hz), 3.97 (3H, s), 7.39 (1H, dd, J = 1.7 and 8.4Hz), 7.64 (1H, s), 7.80 (1H, d, J = 8.6Hz), 7.86 (1H, d, J = 8.4Hz), 8.03 (1H, dd, J = 1.7) and 8.6Hz), 8.57 (1H, s) APCI MASS: m / z = 271 (M + 1)

Preparation 289

To a stirred solution of methyl 6-hydroxynaphthalene-2-; (Carboxylate (3.0 g) in dichloromethane (40 ml) was added alternately diisopropylethylamine (3.9 ml) and triflic anhydride: 7 (3.0 ml) at -40 ° C. After 20 minutes, the mixture was dissolved in a mixture of ethyl acetate and cold 7 'water. The organic layer was separated, washed with brine, dried over magnesium sulfate and dried in vacuo.

The residue was dissolved in piperidine (20 ml) and 1-heptin (4.0 ml) and tetrakis (triphenylphosphine) palladium (O) (0.5 g) were added to the solution. After heating to 85 ° C for 1 hour under a nitrogen atmosphere, the reaction mixture was evaporated in vacuo. The residue was diluted with ethyl acetate, and the solution was washed alternately with hydrochloric acid and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (200 mL) eluting with a mixture of n-hexane and ethyl acetate 7 '(9: 1 / V / V) to give methyl 6- (1-heptynyl) naphthalene-2-7; carboxylate (4.01 g).

NMR (CDCl 3, δ): 0.94 (3H, t, J = 7.1 Hz), 1.30-1.70 (6H, m), 2.46 (2H, t, J = 7.0Hz), 3.97 (3H, s), 7.50 (1H, dd, J = 1.7 and 8.6Hz), 7.80 (1H, 92d, J = 8.6Hz), 7.86 (1H, d, J = 8.6Hz), 8.04 (1H, dd, J = 1.7 and 8.6Hz), 8.55 (1H, s) APCI MASS: m / z = 281 (M + +1). )

The following compound was obtained in the same manner as Preparation 289.

Preparation 290

Methyl 6- (1-hexynyl) naphthalene-2-carboxylate NMR (CDCl 3, δ): 0.97 (3H, t, J = 7.1 Hz), 1.40-1.71 (4H, m), 2 , 47 (2H, t, J = 6.8Hz), 3.98 (3H, s), 7.50 (1H, dd, J = 1.5 and 8.5Hz), 7.79 (1H, d, J = 8.6Hz), 7.85 (1H, d, J = 8.5Hz), 7.92 (1H, s), 8.04 (1H, dd, J = 1.7 and 8.6Hz), 8.55 (1H, s) APCI MASS: m / z = 267 (M + +1).

Preparation 291

To a solution of 4-octylaniline (5 ml) in a mixture of pyridine (12.5 ml) and chloroform (40 ml) was added phenyl chloroformate (2.95 ml) and stirred for 1.5 hours at ambient temperature. The reaction mixture was added to a mixture of water and ethyl acetate. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-octyl-N-; phenoxycarbonylaniline (4.51 g); and (KBr): 3318.9, 1714.4, 1234.2 cm -1; 1 H NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.2Hz), 1.2-1.4 (10H, m), 1.5-1.7 (2H, m), 2.57 (2H, t, J = 7.3Hz), 6.88 (1H, s), 7.1-7.5 (9H, m)::: The following compounds (Preparations 292-299) were obtained in the same manner as Preparation 291.

4- (4-tert-Butoxycarbonylpiperazin-1-yl) -N-phenoxycarbonylaniline IR (KBr): 3309.2, 1743.3, 1658.5, 1197.6 cm 1 NMR (CDCl 3, δ): 1.48 (9H, s), 3.08 (4H, t, J = 5.3Hz), 3.58 (4H, t, J = 5.3Hz), 6.87 (1H, s), 6.91 (2H, d, J = 9Hz), 7.1-7.5 (7H, m) APCI MASS: m / z = 398 (M + H +)

Preparation 293 93 1- (4-Cyclohexylbenzoyl) -2- (4-methoxycarbonylbenzoyl) hydrazine IR (KBr): 3236, 2925, 2852, 1726, 1679, 1637, 1278, 1110 cm -1 NMR (DMSO-d δ): 1.1-1.5 (5H, m), 1.6-2.0 (5H, m), 2.60 (1H, m), 3.90 (3H, s), 7.37 (2H, d, J = 8.0Hz), 7.85 (2H, d, J = 8.0Hz), 8.0-8.2 (4H, m), 10.48 (1H, s), 10 , 68 (1 H, s) APCI MASS: m / z = 381 (M + H) +

Preparation 294 1- [4- (Piperidin-1-yl) benzoyl] -2- (4-methoxycarbonylbenzoyl) hydrazine IR (KBr): 3500, 3286, 2941, 2854, 1712, 1689, 1650, 1606, 1286, 1242-1 cm NMR (DMSO-d6, δ): 1.59 (6H, s), 3.33 (4H, s), 3.90 (3H, s), 6.97 (2H, d, J = 8.8Hz), 7.79 (2H, d, J = 8.8Hz), 8.02 (2H, d, J = 8.4Hz), 8.09 (2H, d, J = 8.4Hz), 10.23 (1H, s), 10.57 (1H, s) APCI MASS: m / z = 382 (M + H) +.

Preparation 295; ', 1- [4- (4-n-Propyloxyphenyl) benzoyl] -2- (4-methoxycarbonylbenzoyl) hydrazine IR (KBr): 3230, 1724, 1679, 1654, 1280, 1108 cm-1: NMR (DMSO-d6, δ): 1.00 3H, d, J = 7.5Hz), 1.76 (2H, tq, J = 6.5 and 7.5Hz), 3.91 (3H, s) , 7.05 (2H, d, J = 8.7Hz), 7.71 (2H, d, J = 8.7Hz), 7.79 (2H, d, J = 8.5Hz), 8.00 ( 2H, d, J = 8.5Hz), 8.05 (2H, d, J = 8.6Hz), 8.11 (2H, d, J = 8.6Hz), 10.60 (1H, s), 10.72 (1H, s) APCI MASS: m / z = 433 (M + H) +: Preparation 296.1- (4-Methoxycarbonylbenzoyl) -2-decanoylhydrazine IR (KBr): 3220, 2919, 2850 1724, 1643, 1600, 1567, 1479, 1284 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.8Hz), 1.2-1.7 (14H, m) ), 2.18 (2H, t, J = 7.4Hz), 3.89 (3H, s), 7.97 (2H, d, J = 8.5Hz), 8.06 (2H, d, ' ': J = 8.5Hz), 9.15 (1H, s), 10.49 (1H, s) APCI MASS: m / z = 349 (M + H +).

Preparation 297 94 1- (4-Methoxycarbonylbenzoyl) -2- (trans-4-n-pentylcyclohexylcarbonyl) hydrazine IR (KBr): 3201, 2923, 2852, 1727, 1600, 1567, 1479, 1282 cm -1 DMSO-d6, δ): 0.86 (3H, t, J = 6.9Hz), 0.9-1.0 (2H, m), 1.1-1.5 (UH, m), 1, 7-1.9 (4H, m), 2.20 (1H, m), 3.88 (3H, s), 7.97 (2H, d, J = 8.6Hz), 8.06 (2H, d, J = 8.6Hz), 9.85 (1H, s), 10.46 (1H, s) APCI MASS: m / z = 375 (M + H +)

Preparation 298 1- [4- (8-Methoxy-octyloxy) -benzoyl] -2- (4-methoxycarbonyl-benzoyl) -hydrazine IR (KBr): 3213, 2935, 2856, 1718, 1600, 1567, 1465, 1282 cm -1 DMSO-d6, δ): 1.2-1.8 (12H, m), 3.21 (3H, s), 3.29 (2H, t, J = 6.4Hz), 3.90 (3H, s), 4.04 (2H, t, J = 6.5Hz), 7.04 (2H, d, J = 8.8Hz), 7.90 (2H, d, J = 8.8Hz), δ, 04 (2H, d, J = 8.7Hz), 8.10 (2H, d, J = 8.7Hz), 10.41 (1H, s), 10.64 (1H, s) APCI MASS: m / z = 457 (M + H +)

Preparation 299; ', 1- (4-Octyloxybenzoyl) -2- (4-methoxycarbonylbenzoyl) -1'-hydrazine V IR (KBr): 3224, 2923, 2854, 1724, 1681, 1643, 1502, 1434, 1282. Λmax 1253, 1106 cm -1: ¹H NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.8 µz), 1.2-1.5 (10H, m), 1.6-1.8 (2H, m), 3.89 (3H, s), 4.04 (2H, t, J = 6.3Hz), 7.04 (2H, d, J = 8.7Hz) 7.90 (2H, d, J = 8.6Hz), 8.03 (2H, d, J = 8.6Hz), 8.10 (2H, d, J = 8.6Hz). ), 10.42 (1H, s), 10.64 (1H, s) APCI MASS: m / z = 427 (M + H +)! (Preparation 300

A solution of methyl 4-n-hexyloxybenzoate 7N (2.00 g) and hydrazine hydrate (4.24 g) in ethanol (10 ml) was refluxed for 6 hours. After cooling, the reaction mixture was poured into water. The precipitate was collected by filtration, washed with water, and dried under a vacuum of Ρ2θ2: 1ΐ3 to give N- (4-n-hexyloxybenzoyl) hydrazine (1.96 g).

IR (KBr): 3311, 2954, 2869, 1623, 1253 cm-1 95 NMR (DMSO-d6, δ): 0.87 (3H, t, J = 6.8Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 4.00 (2H, t, J = 6.5Hz), 4.40 (2H, s), 6.95 (2H, d, J = 8.6Hz), 7.77 (2H, d, J = 8.6Hz), 9.59 (1H, s) APCI MASS: m / z = 237 (M + H) +.

The following compounds (Preparations 301-308) were obtained in the same manner as Preparation 300.

Preparation 301 N- (4-Octylphenyl) -N'-aminourea IR (KBr): 3309.2, 1683.6, 1554.3 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.7Hz), 1.1-1.4 (10H, m), 1.4-1.6 (2H, m), 2.48 (2H, t, J = 8.9Hz), 4, 32 (2H, s), 7.03 (2H, d, J = 8.4Hz), 7.32 (1H, s), 7.38 (2H, d, J = 8.4Hz), 8.50 ( 1H, s)

Preparation 302 N- [4- (4-tert-Butoxycarbonylpiperazin-1-yl) phenyl] -N'-aminourea IR (KBr): 3237.9, 1695.1, 1670.1, 1540.8, 1230.4 cm 1 H NMR (DMSO-d 6, δ): 1.42 (9H, s), 2.97 (4H, t, J = 4.9Hz), 3.44 (4H, t, J = 4.9Hz), 4.30 (2H, s), 6.85 (2H, d, J = 9.0Hz), 7.26 (1H, s), 7.36:, (2H, d, J = 9.0Hz), 8.41 (1H, s) 'Preparation 303; 1-4-Cyclohexylbenzoylhydrazine IR (KBr): 3318, 2925, 2852, 1625, 1606, 1527, 1326 cm -1 1 H NMR (DMSO-d 6, δ): 1.1 -1.5 (5H, m), 1.6-2.0 (5H, m), 2.4-2.6 (1H, m), 4.44 (2H, s), 7.27 (2H) , d, J = 8.2Hz), 7.73 (2H, d, J = 8.2Hz), 9.66 (1H, s) 1 'APCI MASS: m / z = 219 (M + H) +.

Preparation 304: 3 4- (Piperidin-1-yl) benzoylhydrazine IR (KBr): 3263, 2852, 1612, 1504, 1245, 1124 cm -1 1 H NMR (DMSO-d 6, δ): 1.57 (6H, s) , 3.25 (4H, s), 4.35 (2H, s), 6.90 (2H, d, J = 9.0Hz), 7.68 (2H, d, J = 9.0Hz), 9 , 44 (1H, s) APCI MASS: m / z = 220 (M + H) +

Preparation 305 96 4- (4-n-Propyloxyphenyl) benzoylhydrazine IR (KBr): 3350, 3276, 1610, 1494, 1288, 978 cm -1 NMR (DMSO-d 3, δ): 0.99 (3H, t, J = 7.5Hz), 1.75 (2H, tq, J = 6.5 and 7.5Hz), 3.98 (2H, t, J = 6.5Hz), 4.50 (2H, s), 7 , 03 (2H, .d, J = 8.8Hz), 7.65 (2H, d, J = 8.8Hz), 7.69 (2H, d, J = 8.4Hz), 7.88 (2H , d, J = 8.4Hz), 9.79 (1H, s) APCI MASS: m / z = 271 (M + H +)

Preparation 306 4-Methoxycarbonyl-benzoylhydrazine IR (KBr): 3322, 3250, 3018, 1727, 1658, 1621, 1565, 1432, 1280, 1110 cm -1 NMR (DMSO-d 6, δ): 3.87 (3H, s) ), 4.58 (2H, s), 7.93 (2H, dd, J = 8.6 and 3.1Hz), 7.02 (2H, dd, J = 8.6 and 3.1Hz), 9 , 97 (1H, s) APCI MASS: m / z = 195 (M + H +).

Preparation 307

Trans 4-n-Pentylcyclohexylcarbonylhydrazine IR (KBr): 3303, 3199, 2954, 2925, 2850, 1639, 1619, 1533, 1457 cm -1 NMR (DMSO-d 6, δ): 0.8-1.0 (6H) , m), 1.1-1.5 (10H, m), 1.6-2.2 (5H,; v. m), 4.10 (2H, s), 8.85 (1H, s) ) '; APCI MASS: m / z = 213 (M + H +): '(Preparation 308:;; 4- (8-Methoxy-octyloxy) -benzoyl-hydrazine IR (KBr): 3309, 2937, 2852, 1606, 1494, 1253 cm -1) (DMSO-d6, δ): 1.2-1.8 (12H, m), 3.20 (3H, s), 3.25 (2H, t, J = 6.5 Hz), 3.99 (2H) , t, J = 6.5 Hz, 4.39 (2H, s), 6.95 (2H, d, J = 8.8Hz), 7.77 (2H, d, J = 8.8Hz), 9 , 58 (1 H, s) APCI MASS: m / z = 295 (M + H) +

Preparation 309

To a stirred solution of 4-bromo-4'-n-heptylbiphenyl (2.71 g) in tetrahydrofuran (100 mL) was added dropwise a solution of n-butyllithium in a mixture of diethyl ether and n-hexane (1.6M, 5 mL). , 1 mL) at -78 ° C. After stirring at -78 ° C for 30 ml 97 noodles, the resulting mixture was added to a solution of diethyl oxalate (3.4 ml) in tetrahydrofuran (50 ml) at -78 ° C. The resulting mixture was allowed to warm to 0 ° C for about 1 hour, and acetic acid (0.5 mL) was added. Evaporation gave a residue which was dissolved in a mixture of water and ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulfate. Evaporation gave a residue which was chromatographed on silica gel (200 mL) eluting with a mixture of n-hexane and ethyl acetate (10: 0-95: 5, v / v) to give 1-ethyl-2- (4-n-heptylphenyl) ethanedione (2.23 g).

NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.6Hz), 1.10-1.50 (8H, m), 1.44 (3H, t, J = 7.1Hz), 1.50-1.80 (2H, m), 2.66 (2H, t, J = 7.7Hz), 4.47 (2H, q, J = 7.1Hz), 7.20-7.40 (2H, m), 7.50-7.64 (2H, m), 7.64-7.85 (2H, m), 8.00-8.20 (2H, m) APCI MASS: m / z = 353 (M ++ 1)

Preparation 310

To a suspension of sodium hydride (60% in oil, 0.37 g) in tetrahydrofuran (40 ml) was added portionwise 4-acetyl-4'-n-heptylbiphenyl (2.50 g) at ambient temperature. After stirring at ambient temperature for 1 hour, triethylphosphonoacetate (1.9 ml) was added to the solution and the mixture was heated; with reflux for 5 hours. After cooling to ambient temperature, acetic acid (0.53 mL) was added to the mixture and evaporated.

The residue was dissolved in a mixture of water and ethyl acetate.

The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue was chromatographed on silica gel (200 mL) eluting with n-III (hexane: diisopropyl ether (99: 1-20: 1, v / v) to give ethyl (E) -3- [4- (4-heptylphenyl) phenyl] -2-butenoate (2.19 g).

NMR (CDCl 3, δ): 0.88 (3H, t, J = 6.6Hz), 1.13-1.48 (8H, m), 1.48-1.78 (2H, m), 2, 61 (3H, s), 2.65 (2H, t, J = 7.4Hz), 4.22 (2H, q, J = 7.1Hz), 6.20 (1H, t, J = 2.7Hz) ), 7.23-7.28 (2H, m), 7.50-7.63 (6H, m) h / APCI MASS: m / z = 365 (M + +1). Preparation 311

To a solution of 4-bromo-4'-n-heptylbiphenyl (5.1 g) in tetrahydrofuran (60 ml) was added a solution of n-butyllithium 98 in a mixture of n-hexane and diethyl ether (1.6M, 9 7 ml) at -60 ° C. After stirring at -60 ° C for 30 minutes, N, N-dimethylacetamide (4.3 ml) was added and the reaction mixture was allowed to warm to 0 ° C. The reaction mixture was dissolved in a mixture of cold water and ethyl acetate and the pH was adjusted to about 1N with hydrochloric acid. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel (150 mL) eluting with a mixture of n-hexane and ethyl acetate (20: 1, v / v) to give 4-acetyl-4'-n-heptylbiphenyl (1.60 g).

NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.6Hz), 1.05-1.48 (8H, m), 1.48-1.75 (2H, m), 2, 65 (2H, t, J = 7.6Hz), 2.63 (3H, s), 7.20-7.31 (2H, m), 7.52-7.58 (2H, m), 7, 65-7.70 (2H, m), 7.97-8.05 (2H, m) APCI MASS: m / z = 295 (M + 1).

Preparation 312

To a solution of methyl 4- [4- (8-hydroxy-octyloxy) -phenyl] -benzoate (500 mg) and dihydropyran (141 mg) in dichloromethane (15 mL) was added p-toluenesulfonic acid (5 mL). The mixture was stirred at ambient temperature for 10 minutes and diluted with dichloromethane and washed with water and brine. The separated organic layer was dried over magnesium sulfate and evaporated under reduced pressure to give methyl 4- [4- (8-; ', tetrahydropyran-2-yloxy-octyloxy) -phenyl] -benzoate (616 mg).

IR (KBr): 2935, 2856, 1722, 1602, 1438, 1290, 1199 cm -1: 1 H NMR (CDCl 3, δ): 1.3-2.0 (18H, m), 3.3-3. 9 (4H, m), 3.93 (3H, s), 4.00 (2H, t, J = 6.5 Hz), 4.5-4.6 (1H, m), 6.98 (2H, d, J = 8.7Hz), 7.56 (2H, d, J = 8.7Hz), 7.62 (2H, d, J = 8.3Hz), 8.07 (2H, d, J = 8 , 3 Hz)

Preparation 313 I To a solution of titanium (IV) chloride (11.6 g) in dichloro-b "b methane (100 mL) was added 4-n-pentyloxyacetophenone (10.3 g) and methyl 4-formylbenzoate (8, 21 g) in dichloromethane (50 ml) dropwise at 0 ° C. To the mixture was added tri: 11; ethylamine (11.15 ml) in dichloromethane (30 ml). The mixture was stirred at 0 ° C for 30 minutes and diluted. The organic layer was washed with water (four times), brine and dried over magnesium sulfate, the solvents were removed under reduced pressure, and the residue was triturated with isopropyl ether to give a solid which was collected by filtration and dried. 1- (4-methoxycarbonylphenyl) -3- (4-n-pentyloxyphenyl) -1-propen-3-one (4.02 g) was added.

IR (KBr): 2950, 2910, 2863, 1718, 1654, 1606, 1274, 1176 cm -1 NMR (CDCl 3, δ): 0.94 (3H, t, J = 6.9Hz), 1.3-1 , 6 (4H, m), 1.8-2.0 (2H, m), 3.93 (3H, s), 4.04 (2H, t, J = 6.5Hz), 6.97 (2H , d, J = 8.8Hz, 7.60 (1H, d, J = 15.7Hz), 7.68 (2H, d, J = 8.4Hz), 7.80 (1H, d, J = 15.7Hz), 8.0-8.2 (4H, m) APCI MASS: m / z = 353 (M + H +)

Preparation 314

To a solution of titanium (IV) chloride (13.88 g) in dichloromethane (100 mL) was added ethyl 4-acetylbenzoate (11.53 g) and 4-n-pentyloxybenzaldehyde (12.69 g) di chloromethane (50 mL) at 0 ° C. To the mixture was added triethylamine (12.44 mL) in dichloromethane (30 mL). The mixture was stirred at 0 ° C for 30 minutes and diluted with ethyl acetate. The organic layer was washed with water (four times) and brine, and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with n-hexane. The solid was collected by filtration and dried to give 1- (4-n-pentyloxyphenyl) -3- (4-ethoxycarbonylphenyl) -1-propen-3-one (13.45 g).

IR (KBr): 2956, 2929, 2861, 1718, 1656, 1594, 1510, 1272 cm -1 NMR (CDCl 3, δ): 0.94 (3H, t, J = 7.1 Hz), 1.3 -1.9 (9H, m), 4.01 (2H, t, V; J = 6.5Hz), 4.42 (2H, q, J = 7.1Hz), 6.93 (1H, d, J = 8.7Hz), 7.37 (1H, d, J = 15.6Hz), 7.60 (2H, d, J = 8.7Hz), 7.81 (1H, d, J = 15.6Hz) ), 8.03 (2H, d, J = 8.5Hz), 8.16 (2H, d, J = 8.5Hz) M, APCI MASS: m / z = 367 (M + H +) 7 '' The following compound was obtained in the same manner as Preparation 314.

1 * i Preparation 315 ''; 1 Ethyl 4-oxo-1- (4-n-hexyloxyphenyl) piperidine-3-carb; '' '; boxylate; ·.! IR (neat): 1664.3, 1511.9, 1243.9, 1216.9 cm-1 NMR (CDCl3, δ): 0.90 (3H, t, J = 6.5Hz), 1.2- 1.5 (6H, m), 1.32 (3H, t, J = 7.1Hz), 1.65-1.85 (2H, m), 2.51 (2H, t, J = 5.8Hz) ), 3.31 (2H, t, J = 5.8Hz), 3.76 (2H, s), 3.91 (2H, t, J = 6.5Hz), 4.26 (2H, q) , J = 7.1Hz), 6.84 (2H, d, J = 9.2Hz), 6.94 (2H, d, J = 9.2Hz), 12.06 (1H, s) 100 APCI MASS m / z = 348 (M + + H)

Preparation 316

To a solution of 4-n-hexyloxybenzoylhydrazine (1.96 g) and pyridine (0.74 ml) in tetrahydrofuran (20 ml) was added dropwise a solution of terephthalic acid monomethyl ester chloride (1.56 g) in tetrahydrofuran (15 ml). 0 ° C. The reaction mixture was stirred at room temperature for 2 hours and poured into water. The precipitate was collected by filtration and washed with acetonitrile. The residue was dried under reduced pressure to give 1- (4-n-hexyloxybenzoyl) -2- (4-methoxycarbonylbenzoyl) hydrazine (2.99 g).

IR (KBr): 3230, 3023, 2954, 2858, 1724, 1681, 1643, 1280, 1251, 1105 cm -1 1 H NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6, 6Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 3.90 (3H, s), 4.04 (2H, t, J = 6, 4Hz), 7.04 (2H, d, J = 8.7Hz), 7.90 (2H, d, J = 8.7Hz), 8.03 (2H, d, J = 8.4Hz), 8, 10 (2H, d, J = 8.4Hz), 10.42 (1H, s), 10.65 (1H, s) APCI MASS: m / z = 399 (M + H) +.

Preparation 317

A mixture of 1- (4-n-hexyloxyphenyl) -4-piperidone (0.823: g), 1- (4-ethoxycarbonylphenyl) piperazine (0.7 g), and titanium:; Ni (IV) isopropoxide (1.11 mL) was stirred at room temperature.

After 1 hour, the IR spectrum of the mixture showed no ketone linkage and the viscous solution was diluted with absolute ethanol (3 L '). Sodium cyanoborohydride! (0.121 g) was added and the solution was stirred for 3 hours. Water (3 mL) was added with stirring, and the resulting organic precipitate was filtered and washed with ethanol. The filtrate was extracted with ethyl acetate. The organic layer was separated and dried over magnesium sulfate. magnesium | the filtrate was separated by filtration and the filtrate evaporated under reduced pressure to give ethyl 4- [4- [1- (4-n-hexyloxyphenyl) piperidin-4-yl] piperazin-1-yl] benzoate:, (, (331 mg).

3 ": IR (KBr): 1708.6, 1606, 4, 1511.9, 1284.4, 1236.1 cm -1 NMR (CDCl 3, δ): 0.90 (3H, t, J = 6.5Hz) ), 1.2-1.55 (6H, m), 1.37 (3H, t, J = 7.1 Hz), 1.6-1.85 (4H, m), 1.95 (2H, d) , J = 12Hz), 2.41 (1H, m), 3.62 (2H, d, J = 11Hz), 2.75 (4H, t, J = 5.0Hz), 3.35 (4H , t, J = 5.0Hz), 3.58 (2H, d, J = 11Hz), 3.90 (2H, t, J = 6.5Hz), 4.32 (2H, q, J = 7, 1Hz), 6.7-7.0 (6H, m), 7.92 (2H, d, J = 9.0Hz) 101 APCI MASS: m / z = 494 (M + + H).

The following compound was obtained in the same manner as Preparation 317.

Preparation 318 1-tert-Butoxycarbonyl-4- (4-phenylcyclohexyl) piperazine IR (KBr): 1697.1 / 1245.8, 1170.6, 1124.3, 700 cm -1 NMR (CDCl 3, δ): 1 2-1.65 (17H, m), 1.9-2.1 (4H, m), 2.3-2.6 (2H, m), 2.55 (4H, t, J = 5.0Hz) ), 3.44 (4H, t, J = 5.0Hz), 7.1-7.4 (5H, m) APCI MASS: m / z = 345 (M + + H)

Preparation 319

To a suspension of 1- (N, N-dimethylamino) -2- (4-ethoxycarbonylbenzoyl) ethylene (0.742 g) and 4-n-hexyloxybenzamidine hydrochloride (0.847 g) in methanol (10 mL) was added 28% NaOH. trium methoxide in methanol (0.64 mL). The suspension was refluxed for 6 hours and partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with acetonitrile, collected by filtration and dried under reduced pressure to give methyl 4- [2- (4-n-hexyloxyphenyl) pyrimidin-6-yl] benzoate (0.61 g).

: "IR (KBr): 2931, 2861, 1722, 1606, 1558, 1251 cm -1 1 H NMR (CDCl 3, δ): 0.95 (3H, t, J = 6.7Hz), 1.2-1 , 6 (6H, m), 1.8-2.0 (2H, f ': m), 3.97 (3H, s), 4.05 (2H, t, J = 6.5Hz), 7 , 02 (2H, d, J = 8.8Hz), 7.56 (1H, d, J = 5.2Hz), 8.18 (2H, d, J = 8.6Hz), 8.28 (2H, d, J = 8.6Hz), 8.52 (2H, d, J = 8.8Hz), 8.83 (1H, d, J = 5.2Hz) APCI MASS: m / z = 391 (M + + H)

Preparation 320 '<A solution of 1- (4-methoxycarbonylphenyl) -3- (4-n-pentyloxyphenyl) -1-propen-3-one (4.0 g) and hydroxyamine hydrochloride (3.93 g) ) in ethanol (40 ml) was refluxed for 4 hours. The mixture was diluted with ethyl acetate and the organic layer was washed with water (x 2), brine and dried over magnesium sulfate. The solvents were removed under reduced pressure to give; crude oxime. To a solution of the crude oxime in 1,2-dichloroethane (20 mL) was added active manganese (IV) oxide (10.0 g). The reaction mixture was refluxed for 2 hours and filtered. The residue was washed with dichloromethane. The solvents were removed under reduced pressure and 102 residues were triturated with acetonitrile. The solid was collected by filtration and dried to give methyl 4- [3- (4-n-pentyloxyphenyl) isoxazol-5-yl] benzoate (0.98 g).

IR (KBr): 2940, 2871, 1720, 1612, 1278, 1249, 1178, 1108 cm -1 NMR (DMSO-d 6, δ): 0.94 (3H, t, J = 7.2Hz), 1.2 -1.6 (4H, m), 1.7-1.9 (2H, m), 3.95 (3H, s), 4.01 (2H, t, J = 6.5Hz), 6.87 (1H, s), 6.98 (2H, d, J = 8.9Hz), 7.79 (2H, d, J = 8.9Hz), 7.89 (2H, d, J = 8.6Hz) , 8.15 (2H, d, J = 8.6Hz) APCI MASS: m / z = 366 (M + H +).

Preparation 321

To a solution of 4-methoxycarbonylphenylhydroxyiminomethyl chloride (16.98 g) and 4-n-pentyloxyphenylacetylene (18.96 g) in tetrahydrofuran (170 ml) was added triethylamine (14.4 ml) in tetrahydrofuran (140 ml) over For 2 hours at 40 ° C and the mixture was stirred at 40 ° C for 30 minutes. The mixture was diluted with dichloromethane and washed with water and brine. The separated organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with acetonitrile. The precipitate was collected by filtration and dried to give methyl 4- [5- (4-n-pentyloxy-phenyl) -isoxazol-3-yl] -benzoate (24.56 g).

IR (KBr): 2942, 2873, 1716, 1616, 1508, 1280, 1108 cm -1: "NMR (CDCl 3, δ): 0.95 (3H, t, J = 6.9Hz), 1.3-1. , 6 (4H, m), 1.8-2.0 (2H, V: m), 3.95 (3H, s), 4.02 (2H, t, J = 6.5Hz), 6.74 (1H, s), 6.99 (2H, d, J = 8.8Hz), 7.76 (2H, d, J = 8.8Hz), 7.93 (2H, d, J = 8.5Hz) ), 8.14 (2H, d, J = 8.5Hz); ·, APCI MASS: m / z = 366 (M + H +)

Preparation 322

To a solution of N-hydroxy-4-octyloxybenzamidine (1.89 g) in pyridine (10 ml) was added dropwise terephthalic acid monomethyl ester chloride (1.67 g) in tetrahydrofuran (15 ml) at 0 ° C. The mixture was stirred at room temperature for 15 minutes and poured into water. The precipitate was collected by filtration, dried, and dissolved in pyridine (10 mL). The solution was refluxed for 1 hour, f The reaction mixture was diluted with ethyl acetate and washed with 1N HCl; with water and brine. The separated organic layer was dried over magnesium sulfate, and the solvents were removed under reduced pressure. The residue was triturated with acetonitrile and recovered by filtration. The solid was dried to give methyl 4- 103 [3- (4-n-hexyloxyphenyl) -1,2,4-oxadiazol-5-yl] benzoate (2.27 g).

IR (KBr): 2950, 2925, 2863, 1720, 1280, 1255 cm -1 NMR (CDCl 3, δ): 0.92 (3H, t, J = 6.6Hz), 1.2-1.9 (8H) , m), 3.97 (3H, s), 4.03 (2H, d, J = 6.5Hz), 7.00 (2H, d, J = 8.9Hz), 8.09 (2H, d) , J = 8.9Hz), 8.20 (2H, d, J = 6.6Hz), 8.28 (2H, d, J = 6.6Hz) APCI MASS: m / z = 381 (M + H) ) +

Preparation 323

A suspension of 1- (4-n-hexyloxybenzoyl) -2- (4-methoxycarbonylbenzoyl) hydrazine (1.00 g) in phosphorus oxychloride (5 mL) was refluxed for 1 hour. After cooling, the solution was concentrated under reduced pressure. The residue was poured into ice water and extracted with dichloromethane. The organic layer was washed with water, brine and dried over magnesium sulfate. The solvents were removed under reduced pressure. The residue was triturated with acetonitrile, collected by filtration and dried under reduced pressure to give methyl 4- [5- (4-n-hexyloxyphenyl) -1,3,4-oxadiazol-2-yl] benzoate (7 61 mg).

IR (KBr): 2954, 2854, 1724, 1612, 1494, 1280, 1249 cm -1 NMR (CDCl 3, δ): 0.91 (3H, t, J = 6.6Hz), 1.3-1. Δ (6H, m), 1.7-1.9 (2H, δ m), 3.96 (3H, s), 4.04 (2H, t, J = 6.5Hz), 7.02 (2H, d, J = 8.6Hz), 8.07 (2H, d, J = 8.6Hz), 8.19 (4H, m). APCI MASS: m / z = 381 (M + H) +; "The following compounds (Preparations 324-327) were obtained in a similar manner to V: Preparation 323.

; Preparation 324 7.7 Methyl 4- [5- [4- (4-n-propyloxyphenyl) phenyl] -1,3,4-oxadiazol-2-yl] benzoate IR (KBr): 1720, 1614, 1496, 1280 , 1103 cm -1 NMR (CDCl 3, δ): 1.07 (3H, d, J = 7.5Hz), 1.84 (2H, tq, J = 6.5 and .g. 7.5Hz), 3.98 (3H, s), 3.99 (2H, t, J = 6.5Hz), 7.01 (2H, d, J = 8.8Hz), 7.60 (2H, d, J = 8) , 8Hz), 7.73 (2H, d, J = 8.5Hz), 8.19 (2H, d, J = 8.5Hz), 8.22 (4H, s) APCI MASS: m / z = 415 (M + H +)

Preparation 325 104

Methyl 4- [5- (n-nonyl) -1,3,4-oxadiazol-2-yl] benzoate IR (KBr): 2915, 2848, 1724, 1569, 1436, 1413, 1278 cm -1 NMR (CDCl , δ): 0.88 (3H, t, J = 6.4Hz), 1.2-1.6 (12H, m), 1.8-2.0 (2H, m), 2.94 (2H) , t, J = 7.6Hz), 3.96 (3H, s), 8.11 (2H, d, J = 8.8Hz), 8.17 (2H, d, J = 8.8Hz) APCI- MASS: m / z = 331 (M + H) +

Preparation 326

Methyl 4- [5- [4- (8-methoxyoctyloxy) phenyl] -1,3,4-oxadiazol-2-yl] benzoate IR (KBr): 2925, 2858, 1722, 1614, 1280, 1259 cm NMR (CDCl 3, δ): 1.3-1.9 (12H, m), 3.36 (3H, s), 3.37 (2H, t, J = 6.4Hz), 3.97 (3H, s), 4.04 (2H, t, J = 6.5Hz), 7.02 (2H, d, J = 8.9Hz), 8.07 (2H, d, J = 8.9Hz), δ, 20 (4H, s) APCI MASS: m / z = 439 (M + H +)

Preparation 327

Methyl 4- [5- (4-n-octyloxyphenyl) -1,3,4-oxadiazol-2-yl] benzoate IR (KBr): 2923, 2856, 1722, 1614, 1496, 1282, 1103 cm -1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3 97 (3H, s), 4.04 (2H, t, J = 6.5Hz), 7.03 (2H, d, J = 8.7Hz), 1 '8.07 (2H, d, J = 8) , 7Hz), 8.19 (4H, m) 1 APCI MASS: m / z = 409 (M + H +); :: Preparation 328

A suspension of 1- (4-hexyloxybenzoyl) -2- (4-methoxycarbonylbenzoyl) hydrazine (1.0 g) and diphosphorus penta- / sulfide (1.28 g) in tetrahydrofuran (15 mL) was stirred at room temperature. The mixture was diluted with water (30 mL), stirred for 30 minutes and extracted with dichloromethane. The organic layer 7 "was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with acetones-7 on a grill. The solid was collected by filtration and dried under reduced pressure to give methyl 4- [5- (4-n-hexyloxyphenyl) -1,3,4-thiadiazol-2-yl] benzoate (816 mg). IR (KBr): 2925, 2871, 1722, 1608, 1436, 1276, 1106 cm @ -1 105 NMR (CDCl3, δ): 0.92 (3H, t, J = 6.6Hz), 1.3-2. 0 (8H, m), 3.96 (3H, s), 4.03 (2H, t, J = 6.5Hz), 6.99 (2H, d, J = 8.6Hz), 7.95 ( 2H, d, J = 8.4Hz), 8.16 (2H, d, J = 8.4Hz) APCI MASS: m / z = 397 (M + H) +.

The following compounds (Preparations 329-334) were obtained in the same manner as Preparation 328.

Preparation 329

Methyl 4- [5- [4- (8-methoxyoctyloxy) phenyl] -1,3,4-thiadiazol-2-yl] benzoate IR (KBr): 3210, 2935, 2856, 1718, 1600, 1465, 1280, 1110 cm -1 NMR (CDCl 3, δ): 1.3-1.6 (10H, m), 1.7-1.9 (2H, m), 3.33 (3H, s), 3.37 ( 2H, d, J = 6.4Hz), 3.96 (3H, s), 4.03 (2H, t, J = 6.5Hz), 6.99 (2H, d, J = 8.9Hz), 7.94 (2H, d, J = 8.9Hz), 8.07 (2H, d, J = 8.6Hz), 8.16 (2H, d, J = 8.6Hz) APCI MASS: m / z = 455 (M + H +)

Preparation 330

Methyl 4- [5- (4-cyclohexylphenyl) -1,3,4-thiadiazol-2-yl] benzoate: IR (KBr): 2925, 2850, 1716, 1432, 1274, 1108, 997 cm -1 NMR (CDCl 3, δ): 1.2-1.6 (5H, m), 1.7-2.0 (5H, m), 2.58 (1H, m), 3.96 ,; , (3H, s), 7.34 (2H, d, J = 8.2Hz), 7.93 (2H, d, J = 8.2Hz), 8.07 (2H, d, J = 8) , 6Hz), 8.16 (2H, d, J = 8.6Hz); APCI MASS: m / z = 379 (M + H +), 1; Preparation 331

Methyl 4- [5- [4- (piperidin-1-yl) phenyl] -1,3,4-thiadiazol-2-yl] benzoate: IR (KBr): 2940, 2848, 1720, 1602, 1436 , 1415, 1276, 1108 cm -1, NMR (CDCl 3, δ): 1.68 (6H, lev), 3.34 (4H, lev), 3.96 (3H, s), 6.95 (2H) , d, J = 8.7Hz, 7.88 (2H, d, J = 8.7Hz), 8.05 (2H, d, J = 8.6Hz), 8.16-1 (2H, d, J = 8.6Hz) APCI MASS: m / z = 380 (M + H +)

Preparation 332

Methyl 4- [5- (4-n-octyloxyphenyl) -1,3,4-thiadiazol-2-yl] -106 benzoate IR (KBr): 2927, 2858, 1720, 1606, 1434, 1276, 1106 cm 1 NMR (CDCl 3, δ): 0.89 (3H, t, J = 6.8Hz), 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3 , 96 (3H, s), 4.03 (2H, t, J = 6.5Hz), 7.00 (2H, d, J = 8.9Hz), 7.95 (2H, d, J = 8, 9Hz), 8.06 (2H, d, J = 8.4Hz), 8.16 (2H, d, J = 8.4Hz) APCI MASS: m / z = 425 (M + H +)

Preparation 333

Methyl 4- [5- (4-trans-n-pentylcyclohexyl) -1,3,4-thiadiazol-2-yl] benzoate IR (KBr): 2923, 2850, 1722, 1440, 1276, 1110 cm -1 (CDCl 3, δ): 0.89 (3H, t, J = 6.9Hz), 1.0-1.8 (13H, m), 1.92 (2H, d, J = 13.4Hz), 2 , 24 (2H, d, J = 12.2Hz), 3.15 (1H, tt, J = 12.2 and 3.5Hz), 3.95 (3H, s), 8.01 (2H, dd, J = 8.6 and 2.0 Hz), 8.13 (2H, dd, J = 8.6 and 2.0 Hz) APCI MASS: m / z = 373 (M + H +)

Preparation 334

Methyl 4- [5- [4- (4-n-propyloxyphenyl) phenyl] -1,3,4-thiadiazol-2-yl] benzoate IR (KBr): 1720, 1540, 1508, 1282 cm -1. Δ NMR (CDCl 3, δ): 1.07 (3H, t, J = 7.5Hz), 1.85 (2H, m), 3.9-4.1 (5H, v ': m), δ 01 (2H, d, J = 8.8Hz), 7.59 (2H, d, J = 8.8Hz), 7.70 (2H, d, 7t J = 8.4Hz), 8.07 (2H , d, J = 8.4Hz), 8.1-8.2 (4H, m) APCI MASS: m / z = 431 (M + H) + '' Preparation 335

To a suspension of 4-hexyloxybenzoic acid in oxalyl chloride (10 mL) and dichloromethane (10 mL) was added N, N-dimethylformamide (0.1 mL). The mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure to give crude 4-hexyloxybenzoyl chloride. To a suspension of "ethyl 3-amino-4-hydroxybenzoate (733 mg) and triethylamine" (1.38 ml) and 4-dimethylaminopyridine (DMAP, 10 mg) in methylene chloride (10 ml) was added dropwise, of the above-obtained 4-hexyloxybenzoyl chloride in dichloromethane (5 mL) at 10 ° C 1: The reaction mixture was stirred at 10 ° C for 1.5 h and diluted with dichloromethane (20 mL) The solution was washed successively with CH 2 Cl 2 (20 mL) 107 N HCl aq. (20 mL x 2), EHO (20 mL) and brine (20 mL) The organic layer was dried over MgSO 4 and the solvent was removed under reduced pressure Toluene (15 mL) and p- were added to the residue. toluene sulfonic acid (10 mg) The mixture was refluxed for 6 hours and the solvent removed under reduced pressure, the residue was triturated with acetonitrile and the precipitate was collected by filtration and dried over PO 2 to give 2- (4-hexyloxyphenyl) -5-ethoxycarbonylbenzoxazole (0.60 g). .

IR (KBr): 2952, 2871, 1712, 1623, 1500, 1294, 1255 cm -1 NMR (CDCl 3, δ): 0.92 (3H, t, J = 6.6Hz), 1.3-1.6 (9H, m), 1.7-1.9 (2H, m), 4.05 (2H, t, J = 6.5Hz), 4.42 (2H, q, J = 7.1Hz), 7 , 03 (211, d, J = 6.9Hz), 7.57 (1H, d, J = 8.6Hz), 8.08 (1H, dd, J = 8.6 and 1.7Hz), 8.18 (2H, d, J = 6.9Hz), 8.43 (1H, d, J = 1.7Hz) APCI MASS: m / z = 368 (M + H +)

The following compounds (Preparations 336-337) were obtained in the same manner as Preparation 335.

Preparation 336 5-Ethoxycarbonyl-2- (2-octyloxypyridin-5-yl) benzoxazole IR (KBr): 2933, 2858, 1716, 1623, 1604, 1577, 1467, 1290, 1213, 1083, 1 cm -1 NMR (CDCl3, δ ): 0.89 (3H, t, J = 6.7Hz), 1.2-1.5 (10H, m), 1.43 (3H, t, J = 7.1Hz), 1.7-1 , 9 (2H, m), 4.3-4.5 (4H, m), 6.87 (1H, d, J = 8.7Hz), 7.60 (1H, d, J = 8.6Hz) , 8.11 (1H, dd, J = 8.6 and 1.6Hz), 8.37: j '(1H, dd, J = 8.8 and 2.4Hz), 8.45 (1H, d, J = 1.6Hz), 9.03 (1H, d, J = 2.4Hz); APCI MASS: m / z = 397 (M + H +)

Preparation 337; "2- [4- (4-Hexyl-phenyl) -phenyl] -5-ethoxycarbonyl-benzoxazole IR (KBr): 2952, 2871, 1712, 1623, 1500, 1294, 1255, 1024 cm -1 NMR (CDCl 3, δ): 0 , 90 (3H, t, J = 6.6Hz), 1.2-1.5 (6H, m), 1.44 (3H, t, J = 7, 1H z), 1.6-1.8 (2H, m), 2.67 (2H, t, J = 7.3Hz), 4.43 (2H, q, J = 7.1Hz), 7.27 (1H, d, J = 3.7Hz) ), 7.32 (1H, s), 7.5-7.7 (3H, m), 7.77; 1 (2H, d, J = 8.6Hz), 8.12 (1H, dd, J = 8.6 and 1.7Hz), 8.32 (2H, d, J = 8.5Hz), 8.48 (1H, d, J = 1.2Hz) APCI MASS: m / z = 428 ( M + H +)

Preparation 338 108

A suspension of 4- [4- (8-bromooctyloxy) phenyl] benzoic acid (1 g) in 2,6-dimethylmorpholine (3.06 ml) was refluxed for 30 minutes. The reaction mixture was added to a mixture of water and ethyl acetate and the pH was adjusted to 2.0 conc. HCl. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4- [4- [8- (2,6-dimethylmorpholin-4-yl) octyloxy] phenyl] benzoic acid hydrochloride (0.95 g).

IR (KBr): 2939.0, 1704.8, 1606.4, 1189.9 cm -1 NMR (DMSO-d6, δ): 1.12 (6H, d, J = 6.3Hz), 1.2 -1.6 (10H, m), 1.6-1.9 (4H, m), 2.4-2.7 (2H, m), 2.9-3.1 (2H, m), 3 , 8-4.0 (2H, m), 4.02 (2H, t, J = 6.3Hz), 7.04 (2H, d, J = 8.8Hz), 7.68 (2H, d, J = 8.8Hz), 7.75 (2H, d, J = 8.4Hz), 7.99 (2H, d, J = 8.4Hz) APCI MASS: m / z = 440 (M + H +)

Preparation 339

Sodium hydride (60% suspension in mineral oil, 108 mg) was added to ethoxyethanol (10 mL) and the solution was stirred at 60 for 20 minutes. To the solution was added methyl 4- [4- (8-bromooctyloxy) phenyl] benzoate (1.26 g), and the reaction mixture was stirred at 70 ° C for 2 hours. To the reaction mixture was added 10% aqueous sodium hydroxide solution (2.4 mL) and the solution was stirred at 70 ° C for 1 hour.

::; After cooling, the pH of the solution was adjusted to 2.0 with 1N hydrochloric acid. The precipitate was collected by filtration and dried to give 4- [4- [8- (2-ethoxyethoxy) octyloxy] phenyl] -benzoic acid (1.13 g).

IR (KBr): 2933, 2858, 1685, 1604, 1434, 1294, 1132 cm -1 NMR (DMSO-d 6, δ): 1.09 (3H, t, J = 7.0Hz), 1, 2-1.9 (14H, m), 3.2-3.6 (6H, m), 4.01 (2H, d, J = 6.3Hz), 7.04 (2H, d, J = 8 , 8Hz), 7.67 (2H, d, J = 8.8Hz), 7.74 (2H, d, J = 8.5Hz), 7.98 (2H, d, J = 8.5Hz) ', APCI MASS: m / z = 415 (M + H +).

The following compound was obtained in the same manner as Preparation 300.

: 1 Preparation 340 4-n-Pentyloxy-benzoylhydrazine IR (KBr): 3182, 2937, 2869, 1645, 1618, 1571, 1251 cm-1 109 NMR (DMSO-d 6, δ): 0.89 (3H, d, J = 7.1Hz), 1.2-1.8 (6H, m), 4.00 (2H, t, J = 6.5Hz), 4.41 (2H, s), 6.96 (2H, d, J = 8.8Hz), 7.78 (2H, d, J = 8.8Hz), 9.59 (1H, s) APCI MASS: m / z = 223 (M + H +)

The following compound was obtained in the same manner as Preparation 291.

Preparation 341 1- (4-Methoxycarbonylbenzoyl) -2- (4-n-pentyloxybenzoyl) hydrazine IR (KBr): 3234, 2956, 2931, 1724, 1683, 1643, 1610, 1284, 12 53 cm-1 NMR (DMSO) -dg, δ): 0.90 (3H, t, J = 6.9Hz), 1.2-1.5 (4H, m), 1.6-1.8 (2H, m), 3.90 (3H, s), 4.04 (2H, t, J = 6.5Hz), 7.04 (2H, d, J = 8.8Hz), 7.90 (2H, d, J = 8.8Hz) , 8.03 (2H, d, J = 8.7Hz), 8.10 (2H, d, J = 8.7Hz), 10.42 (1H, s), 10.64 (1H, s) APCI- MASS: m / z = 385 (M + H +)

The following compound was obtained in the same manner as Preparation 328.

Preparation 342

Methyl 4- [5- (4-n-pentyloxyphenyl) thiadiazol-2-yl] benzoate IR (KBr): 2940, 2871, 1720, 1606, 1438, 1280 cm -1: NMR (CDCl 3, δ): ° '95 (3H 'J = 7 / 1Hz), 1.3-1.6 (4H, m), 1.8-2.0 (2H, m), 3.96 (3H, s), 4, 03 (2H, t, J = 6.5Hz), 6.99 (2H, d, J = 8.8Hz), 7.94 (2H, d, J = 8.8Hz), 8.06 (2H , d, J = 8.7Hz), 8.16 (2H, d, J = 8.7Hz) APCI MASS: m / z = 383 (M + H +) 1 The following compound was obtained in a similar manner to Preparation 32.

Preparation 343 '/ 4- [5- (4-n-Pentyloxyphenyl) thiadiazol-2-yl] benzoic acid IR (KBr): 2954, 2867, 1687, 1602, 1432, 1294, 1255 cm &lt; 1 &gt; NMR (DMSO-d6, δ): 0.91 (3H, t, J = 7.0Hz), 1.3-1.5 (4H, m), 1.7-1.9 (2H, m), 4.07 (2H, t, J = 6.7Hz), 7.13 (2H, d, J = 8.8Hz), 7.97 (2H, d, '; J = 8.8Hz), δ, 07 (4H, s) 'APCI MASS: m / z = 369 (M + H +)

The following compound was obtained in the same manner as Preparation 49.

Preparation 344 110 1- [4- [5- (4-n-Pentyloxy-phenyl) -thiadiazol-2-yl] -benzoyl] -benzotriazole-3-oxide IR (KBr): 2948, 2873, 1770, 1602, 1257, 1232 cm -1 NMR (CDCl 3, δ): 0.95 (3H, t, J = 7.1 Hz), 1.3-1.6 (4H, m), 1.8-2.0 (2H, m), 4.04 (2H, t, J = 6.5Hz), 7.01 (2H, d, J = 8.1Hz), 7.4-7.7 (3H, m), 7.97 (2H, d, J = 8.1Hz), 8.12 (1H, d, J = 8.2Hz), 8.24 (2H, d, J = 8.0Hz), 8.40 (2H, d, J = 8.0Hz) APCI MASS: m / z = 486 (M + H +)

Preparation 345

To a solution of 4-bromobenzaldehyde oxime chloride (647 mg) and 4-n-pentyloxyphenylacetylene (650 mg) in tetrahydrofuran (7 ml) was added dropwise triethylamine (0.5 ml) in tetrahydrofuran (5 ml) at 40 ° C. The solution was stirred at 40 ° C for 30 minutes, poured into water and extracted with ethyl acetate. The organic layer was washed with Η20: 1ΐ3, saturated brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with acetonitrile. The precipitate was collected by filtration and dried to give 4- [5- (4-n-pentyloxy-phenyl) -isoxazol-3-yl] -bromobenzene (0.59 g).

IR (KBr): 2948, 2867, 1612, 1430, 1255 cm -1 NMR (CDCl 3, δ): 0.95 (3H, t, J = 6.9Hz), 1.3-1.6 (4H, m) ), 1.7-1.9 (2H, '1' m), 4.01 (2H, t, J = 6.5Hz), 6.66 (1H, s), 6.98 (2H, d, J = 8.8Hz), 7.60 L / (2H, d, J = 8.6Hz), 7.7-7.9 (4H, m), i: APCI MASS: m / z = 388 (M + H +)

Preparation 346

To a suspension of 4- [5- (4-n-pentyloxyphenyl) -isoxazol-3-yl] bromobenzene (386 mg) in tetrahydrofuran (5, 1 mL) was added 1.55 M n-butyllithium in hexane (0.84 mL). At -40 ° C under a stream of ^, and the solution was stirred for 1 hour at -40 ° C. Crushed dry ice (1 g) was added to the solution and the suspension was stirred for 1 hour at -40 ° C. The suspension was diluted with H 2 O and acidified with IN hydrochloric acid. The precipitate was collected. filtration and drying to give 4- [5- (4-n-pentyloxy-phenyl) -isoxazol-3-yl] -benzoic acid (312 mg).

IR (KBr): 2939, 2867, 1681, 1614, 1429, 1255, 1178, 821 cm -1 NMR (DMSO-d6, δ): 0.91 (3H, t, J = 7.1 Hz), 1, 3-1.5 (4H, m), 1.6-1.8 (2H, m), 4.04 (2H, t, J = 6.5Hz), 7.11 (2H, d, J = 8 , 9Hz), 7.54 (1H, s), 7.85 (2H, d, J = 8.9Hz), 7.98 (2H, d, J = 8.6Hz), 8.11 (2H, d) , J = 8.6Hz) APCI MASS: m / z = 352 (M + H +) The starting compound in the following Examples 1 to 117 and the target compounds (1) to (122) and (124) in the following Examples 1 to 122 and 124 are illustrated below chemical formulas.

Starting compound (same as in Examples 1 to 117)

HO OH

HO O ^ - / 1 ^ —N H) \ / f — nh2 '-N \ —0

H0. 7 == 0 HN OH

\> f H

// NH 0 = (CH, H, N n -, / \ 2 O- \ n- \ HO) -NH / \ _ ^ ΌΗ

Il = (° H °:; Nao-s-o -) /; 111 o / /

HO

112

Target compounds (1) to (122) and (124) HO OH HO O \ - / h. * '—N \ = 0

H0, V = ° HN OH

^ ', NH 0 == /' OH o H2N 0 = /

HO) -NH / V

\ / \ / Ny well

O / = / OH O

NaO-S-O - (\ j)

Il

o / -

HO

In the following examples, the target compound (X) [e.g. target compound (1)] refers to Example (X) [e.g. example (1)].

Ex. R1 113

1 I

^ BT ^ CK ^ -O- (CH2) 7CH3 2 - CO- ^ ^) -] / \ r- ^) -0 - (ch2) 7 ch3 3 -COH ^ ^ CH2) 8 ~ \ 4 (CH2) 7CH3 5 - cA ^ TVo - (CH2) n ch3 6 A Jn.

"J · 0 — C Ό- (CH2) 7CH3; '' · o .. 7 -CO-O- ^ ^) - 0- (ch2) 7ch3 \ 8 -C0-0-CH2-Μ 7 = λ ^ = \ V-0- (CH 2) 6 CH 3

Ex. R1 114 o- (ch2) 4ch3 9 / Γ \ _ -co-v y — o- (ch2) 4ch3 10 -c ° m (ch2) 7ch3 11 r ~ ^ Vo- (ch2) 4ch.

-co \ / \ / ^ 4 J

(CH2) 7ch3 12 -co-Ci- / δ., 0- (CHq) 7CHn s .1X0:.: 0 1 ", _A = p (CH2) BCH3: -« _coryJ> (ch2) 5ch3: ¾ 15 -. co ^ fyi 115

Ex. R1 16 ^^ -0- (CH2) 4CH3 17 / H ~ (CH2} gCH3 18 / ^ \ ^ ~ (CHS} 4 ° Η3 19 ^ y ~ ^ \ /) ~ (cH2} 4 ° η3 20 ~ ^ - 0- (ch2) 6ch3 22 -co-ry ^ y (CH2) 5cH3 'i 23 / \;: 2J -CO- / ~ N \ / N \ / ° ~ (CH5) 5CH3 24 _ _ ,,: main product - CO 2 - (CH 2) q OCH 3

Ex. By-product R11 116 24 - CO - ^ (CH21 6 - CH ° C122 25 -co (CH2> 4CH3 26 - "OOomch2) 7ch3 27 -co-ch2-o - <^ o- (ch2) 7ch3 28 -CO- / ' tsi-c - / \ - Λ:, \ - / U ^ = / yO- (CH2) 6CH3 .CH2) 8CH3 29 -CO- / Vn '3 ° // \ -co- ^ Vo- (ch2) 7ch3 - CO- C Ξ Cf ^ Y ^ l

... V 3i L II jI

- ^^ - ^^ 0- (ch2) 6ch3

Ex. R1 117 -CO-NV V-λ 32 H \ / \ v X = <yO- (CH2) 6CH3 33 // // -CO-NC / \ / -0- (CH2) 6CH3 34 // \ // \ -co-c = c- / Vc y— (ch2) 4ch3 35 // \ // \ -co - {/ y-if y— (ch2) 6ch3 Λ ^: ,, 37 -CO ^ N _ ^^ J - (CH2) 7CH3 - 3 8 _ _ _ main product -CO / ~ ^ CH2 ^ 7QCH3

Ex. R1 118 38

by-product _CQ_ ^ r ~ y__N ^ \ ^^ y.0 / VW

-CO-Q) -N Ν-Η \ (CH2) 6CH3 40 - CO -t / \ r - ^) - 0 / νΛ ^ 41 / ~ \ / \ \ 41 -C0 - <^ -NN-J-0 - (CH 2) 4 CH 3: 42

;:; product mixture _ (^, g_ ^ N

: '._ ^ ch-, 43 jT ~ \ / ~ \ / \ -C0 - <^ y ^ ^ -0- (CH2) q — 0; , ~ _ X ~ ^ -CH3:: 44 jf ~ \ / \ -co-c y-N N-C V-0- (CH2) 7CH3 \ - / \ == /

Ex. R1 119 45 "co 46 // \ / T ~ \ if \ -coy— (fy— / Vo- (ch2) 3ch3 4V -C0 - <^ Y - <^^> - 0- (CH2) 6CH3 48 co I y— (ch2'7ch3 5 ° // \ // \ // \ -co-v y— / y— / yo- (ch2) 3ch3 51 jT \ / ~ \ / ~ \ -co-v y— / y - o- (ch2) 5-o— (fy

Ex. R1 120 52 / - \ N "N \ ft-λ -co— / / - / / ~ ° ~ (ch2) 5ch3 53 Λ \ h Λ / \ -CO - {/ / \ s / \ V ° - (CH2 ) 5CH3 -co —— / \ —o- (ch2) 7ch3 54 N — N v = ^ ch3 55 / / sv /) \ ,, -CO — O - \ / o- (ch2) 4ch3

,:, \ = J N_N \ = J

: 1: H

: Γ: 56 r \ - CO ^ / ^ JH ^ Jr0 · (CH2) 3 CH3 121

Ex. R1 57 NH (Z) ^ -O- (ch2) 4ch3 NH (Z) 58 I .-.

C0 \ A / T \ V-o- (ch2) 7ch3 ®H (Z) <59 -CO. / L // \ y-o- (CH 2) 7ch3

Ex. R1 122 ι-Ο 60 12CH3

OH

HJH (Z) 61 f -co ^ X.

^ (CH 2) 15 OCH 3 CH-,) η «CH-, 62 -CO ^ 2 12 3

? H

/ (CH2) iOCH3 63 / = <- CO ch3 64 _ _: '"main product -C0 - <^ J ^ 1ST— ^ ^ -0- (CH2) 8OCH3:' ,, 64 T; by-product -C0 - <^ ^> - ^ ^ ΝΗ0 οΛΛΛΑ

:, J F

65 / X / "Λ _Γ ~ \,, -C0 - <^ J) _ Ή— V __ / —O" CH2 5CH3

Ex. R1 123 66

Cl / \ / Γ ~ \ - CO pN N — y — ο - (CH2) 5 CH3 _C0 ^ A_n ^ A ν ^ λ 67 \ = / V- / W_ 68 -C0 - <^ -1 / ^ N- ^ VO- (CH2) 5CH3 N-NV— / \ == / 69 -CO-l / ^ ^ -0- (CH2) 5CH3 ::: 1 70 - «Ο ^ Ο'Ο ^ Ο

:, / \ / "A

71 ~ C0 \ __ v— \ / \ ,,: 1 / ~~ \ / \ _ / \ jf ~ \ 72 ~ co —N N y — Cj

Ex. R1 124 73 -CO t / ^ V- ^ - ° - (CH2) 5CH3 74 -co— ^ ......... * (ch2) 4ch3 _co / "Λ 75 v = / 'v — o- (ch2) 8och3 76 ^ ^ ^ ^ ^ CH2 ^ 6CH3 ,, -CO ch3;: 77 / Ά / ^ Λ / s. J! η — e? - (chj 8ch3

-CO \ / \ / ^ b J

Ex. R1 125 79 v_ / ~ \ -co Z 'v— / V- (ch2) 6ch3

OH

80 ~ C ° \ A / \ / ~ {Y - \ = / 0 81 - (CH 2) 6 CH 3

Y; - <f ^ A

; ': 7 82 ^ = / y— (ch2) 5ch3 83 ^ / ~ \ / ^ 0 / V ^ V-voch3

Ex. R1 126 84 "m> - <I": 87, ^ 33 {3 · 15 ·· ^ ':::' 88 -c33hi: #? V33H0'1CH2> 5CH3 \ = / n — N \ = /

B

Ex. R1 127 89 -CQ - <^ ^ -rVo- (CH2) 6OCH3 / - \ N "N \, ΓΛ 90 -CO- / \ - / / \ 91 7-K 7-0- (CH0), CH, - CO \ / \ / ^ 3!. 92 _αο_ ^ Λ Vy ^ y ^ y

r · 93 N

; T; -GO- / ^ -Q- (Ch 2) 2 CH 3 94 -CO- / V / o (CH 2) 8 CH 3

Ex. R1 128 95 // \ / N \ // \ - CO— / / \ j] \ / - ° ~ (CH2) 5CH3

^ = /. 0 — N \ = S

/ - \ N "N \ / r ~ \ 96 -CO- / Η5> Λ-λ0- {™ 2> 7 ™ 3 97 / \ W ^ N \ / \ - CO - / / \ / ...... ... (CH2} 4 CH3:, 98 -CO-ft 'V - ^^ 0_ (CH2) 4CH3 .:. \ = / O-n \ = y \' 99 / -Λ NN λ :: - CO- ^ -O- (CH 2) q OCH 3

100 _co _ ^^ y_ ^ o- ^ yQ

Ex. R1 129) -v N — N ___ 101 if // \\ i / \ -co-r y —— r y — o— (ch2) 7ch3

102 / r— ^ r ^ H

-CO - {/ V — U JL if \ \ / N NJ '0- (CH2) 5CH3 103 / T \ f ~ \ ^ o ^ \ -co-v y — c Vo- (ch2) 104 \ if \ / \ -co - <^ / \ / (CH2) 7 ~ n ~ n \ _ /; '105 \ - ~ ^ \ - o- (CH2) 6CH3; 1 \ = - N' - '\ = /

Ex. Ri 130 106 / ~ \ / ~ \ / T \, 'CO (¾) 8OCH3

107 / - \ / f ~ A

-CO- (1-CH2) 2CH3108 -CO- (N-CH2) 6CH3 -CO- (f--o- (CH2) 7CH3: 7,109 W = = ;, 7,101 - CO-- ^ - / - V - (CH 2) 4ch 3 '111 (CH 2) 7 OCH 3 131

Ex. R1 112 // - λ // - \ / - \ -CO— ^ ^ (CH2) 80— {\ 113

^ IST

I, (CH 2) 9 CH 3 114 -CO - ^ - O - (CH 2); ; , 115 -co-Q - ^ - 0- (ch2) 5och3

_co _ ^ \ y v / ~ V / ~ A

116 \ / v // \ / \ / \ V = l / N — N V = y '-' 117 λΑ // \ jT \ -co V y — c y — c y — o— (ch2) 5och3

Ex. R1 132 118 118 ψ2 -co. A.

^^ C.h.2) 15o.ch3 ψ2 CO '^ K ^^ y ^ y ~ o- (CH2) 4ch3 ¥ H2 120 | : ..: i ¥ h2 '1 121 1 i:; co ^ Q.o, CH2) 7ch3 -CO ^ ^ -0- (ch2) 4ch3 "I 122

Ex. Target Compound 133

HO OH

123 »c r * 3 Vj μΓ ° X3-o- <ch2,7ch3

HO Wo H N OH

V >> 0> <CH3 H2N 0 = /

HO \ -NH / V

\ / Νγ''Λ'ν / Χ> Η 0 / = / OH ö HO — S-0-ά λ »ys

HO

Ex. R1 124 f / -λ / N ~ "N / - \ ° - {c" 2 '«CH3

Example 1 To a solution of the starting compound (1 g) and 1- (6-octyloxymethylpicolinoyl) benzotriazole-3-oxide (0.399 g) in N, N 1 -dimethylformamide (10 ml) was added 4- (N, N-dimethyl) -amino) -pyridine (0.140 g) and stirred for 12 hours at ambient temperature. The reaction mixture was made powdered with ethyl acetate. The precipitate was collected by filtration and dried under reduced pressure. The powder was dissolved in water and column chromatographed with an ion exchange resin. (DOWEX-50WX4 (Trademark: manufactured by Dow Chemical), eluting with water. The fractions containing the target compound were combined and column chromatographed with ODS (YMC-gelODS-AM2S-50) (Trademark: manufactured by Yamamura Chemical Lab.) Eluting with 50% aqueous methanol. .

134

The fractions containing the target compound were combined and evaporated under reduced pressure to remove methanol. The residue was lyophilized to give the target compound (1).

IR (KBr): 3347, 1664, 1629, 1517 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.98 (3H, d, J = 6 , 7Hz), 1.09 (3H, d, J = 6.0Hz), 1.2-1.47 (10H, m), 1.47-1.67 (2H, m), 1.67-2 , 06 (3H, m), 2.06-2.5 (4H, m), 3.19 (1H, m), 3.53 (2H, t, J = 6.4Hz), 3.5-3 , 85 (2H, m), 3.85-4.7 (13H, m), 5.35 (1H, m), 5.56 (1H, d, J = 5.7Hz), 6.73 (1H , d, J = 8.3Hz), 6.83 (1H, d, J = 8.3Hz), 6.89 (1H, s), 7.05 (1H, s), 7.11 (1H, s) ), 7.32 (1H, m), 7.43 (1H, d, J = 8.5Hz), 7.63 (1H, d, J = 7.3Hz), 7.85-8.13 (4H , m), 8.66 (1H, d, J = 7.8Hz), 8.84 (1H, s) FAB MASS: m / z = 1228 (M + + Na)

Elemental Analysis calculated for C 50 H 34 N 4 O 4 SNa N 2 O 4: C 45.49, H 6.44, N 9.59 Found: C 45.89, H 6.52, N 9.69.

The target compounds (2) to (25) were obtained according to Example 1.

Example 2 IR (KBr): 3353, 1666, 1510, 1236 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.96 (3H, d, J = 6.7Hz), 1.06 (3H, d, J = 5.8Hz), 1.2-1.5 (10H, m), 1.55-2.05 (5H, m), 2.11 -2.7 (4H, m), 3.0-3.3 (5H, m), 3.3-3.5 (4H, m), 3.6-4.5 (15H, m), 4 , 6-5.6: (12H, m), 6.6-7.2 (10H, m), 7.2-7.5 (3H, m), 7.81 (2H, d, J = 8 , 8Hz): 8.05 (1H, d, J = 8.7Hz), 8.28 (1H, d, J = 8.7Hz), 8.41 (1H, d, J = 6.7Hz), : v, 8.84 (1H, s). FAB MASS: m / z = 1373 (M + + Na).

Elemental Analysis calculated for C 6 H 83 N 10 O 2 SNa 4H 2 O: C 50, 63, H 6, 44, N 9, 84 Found: C, 50.59; H, 6.59; N, 9.79.

Example 3 IR (KBr): 3350, 1664, 1627, 1047 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.6Hz), 1.08 (3H, d, J = 5.7Hz), 1.15-1.53 (8H, m), 1.55-2.1 (9H, m), 2.1-2.45 (3H, m), 2.5-2 , 7 (1H, m), 3.18 (1H, m), 3.6-3.83 (2H, m), 3.83-4.6 (17H, m), 4.7-5.4 (1H, m), 5.51 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.2Hz), 6.83 (1H, d, J = 8.2Hz) , 6.85 (1H, s), 7.03 (2H, d, J = 8.4Hz), 7.05 (1H, s), 7.30 (1H, s), 7.2-7.5 (2H, m), 7.67 (2H, d, J = 8.4Hz), 7.71 (2H, d, J = 7.4Hz), 7.94 (1H, s), 7.96 (2H) , d, J = 7.4Hz), 8.06 (1H, d, J = 8.0Hz), 8.25 (1H, d, J = 6.7Hz), 8.50 (1H, 135s), 8.74 (1H, d, J = 6.7Hz), 8.84 (1H, s) FAB MASS: m / z = 1356 (M + + Na)

Elemental Analysis calculated for C15 H20 N3 O4ScNa.sub.HgO C 49.53, H 6.02, N 10.95 Found: C 49.26, H 6.22, N 10.77.

Example 4 IR (KBr): 3350, 1660, 1631, 1047 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.9Hz), 0.97 (3H, d, J = 6.6Hz), 1.09 (3H, d, J = 5.3Hz), 1.2-1.5 (10H, m), 1.37 (6H, s), 1.55-2.0 (5H, m), 2.1-2.6 (4H, m), 3.16 (1H, m), 3.73 (2H, m), 3.89 (2H, t, J = 6.3Hz) ), 3.95-4.49 (1H, m), 4.68-5.21 (10H, m), 5.25 (1H, d, J = 4.1Hz), 5.53 (1H, d) , J = 5.7Hz), 6.73 (1H, d, J = 8.2Hz), 6.75-6.85 (4H, m), 6.91 (1H, d, J = 8.2Hz) , 7.05 (1H, s), 7.15 (1H, s), 7.3-7.5 (2H, m), 7.9-8.2 (3H, m), 8.84 (1H , s) FAB MASS: m / z = 1271 (M + + Na)

Elemental Analysis calculated for C53H77NeO23SNa-4H2O C 48.18, H 6.48, N 8.48 Found: C 48.04, H 6.51, N 8.38.

Example 5 IR (KBr): 1666, 1629, 1222 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.6Hz), 0.9-1.12 (6H, m) ), 1.12-1.52 '(13H, m), 1.52-1.93 (5H, m), 2.08-2.55 (4H, m), 3.16 (1H, m) , 3.6-3.5 5.3 (26H, m), 5.49 + 5.54 (1H, d, J = 5.8Hz, diastereomeric mixture): v, 6.60-7.1 (7H , m), 7.04 (1H, s), 7.1 (1H, m), 7.2-7.5 (2H, m), 7.9-8.43 (3H, m), δ , 83 (1H, s) FAB MASS: m / z = 1257 (M + + Na): Elemental Analysis calculated for C52H75N8023SNa-3H2O: C 48, 44, H 6, 33, N 8, 69 Found: C 48 , 16, H, 6.51, N, 8.53. Example 6 IR (KBr): 3349, 1666, 1629, 1259 cm-1 57 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.9 (3H, d, J = 5.7Hz), 0.96 75 (3H, d, J = 6.7Hz), 1.1-1.55 (19H, m), 1.55-2.0 (5H, m), 2.0-2.47 (4H, m), 2.65-3.25 (3H, m), 3.5-5.13 (27H, m) ), 5.17 (1H, d, J = 3.2Hz), .7 5.24 (1H, d, J = 4.5Hz), 5.38 (1H, d, J = 5.9Hz), 6 , 5-6.9 (5H, m), 6.9-; 7 7.1 (3H, m), 7.2-7.46 (2H, m), 7.7-8.1 (3H) , m), 8.83 (1H, s) FAB MASS: m / z = 1368 (M + + Na)

Elemental Analysis calculated for C CHH ^ NNgC ^ ^Na · S ^O O requires C, 48.50; N, 6.60; N, 8.78 Found: C, 48.47; H, 6.83; N, 8.78.

Example 7 136 IR (KBr): 3350, 1666, 1502, 1199 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.6Hz), 0.97 (3H, d, J = 6.7Hz), 1.06 (3H, d, J = 5.7Hz), 1.2-1.5 (10H, m), 1.55-2.0 (5H, m), 2, 1-2.6 (4H, m), 3.17 (1H, m), 3.7-4.5 (15H, m), 4.7-5.22 (10H, m), 5.24 ( 1H, d, J = 4.4Hz), 5.60 (1H, d, J = 5.9Hz), 6.68-7.03 (8H, m), 7.04 (1H, s), 7, 2-7.42 (2H, m), 7.85-8.1 (3H, m), 8.83 (1H, s) FAB MASS: m / z = 1229 (M + + Na)

Elemental Analysis calculated for C20 H25 N4 O4 N2 O3 S4 O4: C, 46.29; H, 6.29; N, 8.64 Found: C, 46.39; H, 6.05; N, 8.72.

Example 8 IR (KBr): 3350, 1666, 1631, 1513 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.2Hz), 0.97 (3H, d, J = 6.7Hz), 1.04 (3H, d, J = 5.7Hz), 1.2-1.58 (8H, m), 1.58-2.0 (5H, m), 2 , 0-2.6 (4H, m), 3.17 (1H, m), 3.6-4.5 (15H, m), 4.63-5.33 (13H, m), 5.53 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.2Hz), 6.82 (1H, d, J = 8.2Hz), 6.84 (1H, s) , 6.95-7.52 (7H, m), 7.66 (1H, d, J = 7.6Hz), 7.7-7.9 (3H, m), 8.05 (1H, d, J = 9.1Hz), 8.15 (1H, d, J = 7.6Hz), 8.85 (1H, s): FAB MASS: m / z = 1279 (M + + Na) 1 "! Elemental Analysis for C54H73N8023SNa-5H2O: C 48.14, H 6.21, N 8.32 'found: C 48.43, H 6.28, N 8.30.

Example 9: 'IR (KBr): 3347, 2956, 1664, 1633, 1508, 1444, 1268,' ': 104-17 cm -1, NMR (DMSO-d 6, δ): 0.9-1 , 1 (9H, m), 1.06 (3H, d, J = 5.9Hz), 1.3-1.5 (8H, m), 1.6-2.0 (7H, m), 2 , 1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 1; "(1H, m), 3.6-4.4 ( 17H, m), 4.7-5.0 (8H, m), 5.09 (1H, d, J = 5.5Hz), 5.16 (1H, d, J = 3.1Hz), δ, 24 (1H, d, J = 4.5Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (2H, m), 6.98 (1H, d, J = 8.3Hz), 7.05 (1H, d, J = 1.7Hz), 7.3 -: t: 7.6 (5H, m), 8.08 (1H, d, J = 8, 9Hz), 8.25 (1H, d, J = 8.4Hz), 8.54 (1H, d, J = 7.5Hz), 8.83 (1H, s) FAB MASS: m / z = 1257 (M + + Na) 137

Elemental Analysis calculated for C52H75N8023SNa-4H2O C 47.78, H 6.40, N 8.57 Found: C 47.88, H 6.71, N 8.53.

Example 10 IR (KBr): 3350, 2931, 1664, 1625, 1529, 1440, 1276, 1226, 1047

CirT1 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6.8Hz), 0.97 (3H, d, J = 6.7Hz), 1.12 (3H, d, J = 5.9Hz), 1.2-1.5 (10H, m), 1.6-2.1 (5H, m), 2.1-2.4 (4H, m), 3.1-3, 3 (1H, m), 3.5-4.6 (15H, m), 4.7-5.0 (3H, m), 5.0-5.2 (7H, m), 5.27 ( 1H, d, J = 4.4Hz), 5.55 (1H, d, J = 5.7Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H , m), 7.0-7.2 (4H, m), 7.3-7.6 (2H, m), 7.90 (1H, d, J = 8.8Hz), 8.0-8 , 2 (2H, m), 8.8-8.9 (2H, m), 9.06 (1H, d, J = 7.2Hz) FAB MASS: m / z = 1281 (M + + Na).

Elemental Analysis calculated for C53H71N8024SNa-5H2O C 47.18, H 6.05, N 8.30 Found: C 46.97, H 6.27, N 8.22.

Example 11 NMR (DMSO-d6, δ): 0.87-1.05 (6H, m), 1.10 (3H, d, J = 5.7Hz), 1.3-1.5 (4H, m) ), 1.6-1.9 (5H, m), 2.2-2.5 (3H, m), 2.6 (1H, m), 3.1-3.2 (1H, m), 3.7-4.1.5 (15H, m), 4.8-5.1 (8H, m), 5.09 (1H, d, J = 5, 64Hz), 5.16 "(1H, d, J = 3.2Hz), 5.26 (1H, d, J = 4.2Hz), 5.52 (1H, d, J = 6.0Hz), 6.73: I: (2H, d, J = 8.4Hz), 6.8-6.9 (2H, m), 7.0-7.1 (3H, m), 7.2-7.4 (4H, m), 7.6- 7.8 (6H, m), 8.11 (1H, d, J = 8.4Hz), 8.29 (1H, d, J = 8.4Hz), 8.51 (3, 1H, d, J = 7.7Hz), 8.85 (1H, s) FAB MASS: m / z = 1273 (M + + Na); "Elemental analysis calculated for C 55 H 71 N 8 O 22 SNa-4H 2 O: 49 C 49, 92, H 6, 02, N, 8.47 Found: C, 49.79; H, 6.14; N, 8.45. '' Example 12 IR (KBr): 3330, 2929, 1670, 1629, 1533, 1440, 1280, 1226, 1045, 804 '. '! -1 cm t ': NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.97 (3H, d, J = 6.7Hz), 1.08 (3H , d, J = 5.9Hz), 1.2-1.6 (10H, m), 1.6-2.0 (5H, m), 2.1-2.5 (4H, m), 3.1-3.3 (1H, m), 3.6-4.5 (15H, m), 4.8-5.1 (9H, m), 5.17 (1H, d, 1H). J = 3.0Hz), 5.25 (1H, d, J = 4.5Hz), 5.56 (1H, d, J = 5.6Hz), 6.73 (1H, d, J = 8, 2Hz), 6.83 (1H, d, J = 6.8Hz), 7.1-7.2 (3H, m), 7.3-7.5 (3H, m), 7.85 (1H , d, J = 8.8Hz), 8.0-8.2 (3H, m), 8.84 (1H, s), 8.96 (1H, d, 138 J = 7.2Hz) FAB MASS : m / z = 1269 (M + + Na)

Elemental Analysis calculated for C52H71N8022S2Na, 4H2O C 47.34, H 6.04, N 8.49 Found: C 47.21, H 5.96, N 8.41.

Example 13 IR (KBr): 3345, 2927, 1664, 1629, 1515, 1442, 1274, 1047 cm -1 NMR (DMSO-d 6 / δ): 0.85 (3H, t, J = 6.7Hz), δ , 97 (3H, d, J = 6.7Hz), 1.10 (3H, d, J = 5.9Hz), 1.2-1.4 (10H, m), 1.5-2.5 ( 8H, m), 2.46 (3H, s), 2.69 (2H, t, J = 7.7Hz), 3.1-3.4 (2H, m), 3.6-4.5 ( 17H, m), 4.8-5.2 (8H, m), 6.7-7.0 (3H, m), 7.05 (1H, d, J = 1.7Hz), 7.14 ( 1H, s), 7.3-7.6 (5H, m), 8.0-8.2 (2H, m), 8.47 (1H, d, J = 7.0Hz), 8.84 ( 1H, s) FAB MASS: m / z = 1251 (M + + Na)

Elemental Analysis calculated for 053-73-80223-3.3-320: C 49.61, H 6.21, N 8.73 Found: C 49.88, H 6.44, N 8.74.

Example 14 IR (KBr): 3340, 1672, 1627, 1542, 1513, 1440, 1268, 1045 cm -1 NMR (DMSO-d 6, δ): 0.84 (3H, t, J = 6.7Hz), δ , 94 (3H, d, J = 6.7Hz), 1.07: (3H, d, J = 6.0Hz), 1.2-1.4 (12H, m), 1.6-2.0 (5H, m), 2.1-2.4 (3H, m), 2.6 (1H, m), 2.96 (2H, t, J = 7.4Hz), 3.1-3.3 (1H, m), 3.6-4.5: V. (13H, m), 4.7-5.2 (11H, m), 5.50 (1H, d, J = 5.7Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (2H, m), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.72 (1H, d, J = 8.5Hz), 7.91 (1H, d, J = 8.4Hz), 8.05 (1H, d, J = 8.4Hz), 8.2 -8.4 µ ··· (1H, m), 8.80 (1H, d, J = 7.7Hz), 8.83 (1H, s) FAB MASS: m / z = 1252 (M ++ As)

Elemental Analysis calculated for C52H72N9022SNa-6H2O C 46, 67, H 6.33, N 9.42 &lt; 1 &gt;: found: G 46.72, H 6.53, N 9.45, I, Example 15. IR (KBr): 3350, 2935, 1664, 1627, 1517, 1446, 1251, 1045 cm -1 NMR (DMSO-d 6, δ): 0.90-1.1 (6H, m), 1.10 (3H) , d, J = 5.9Hz), 1.2-1.4 (6H, m), 1.6-2.4 (8H, m), 2.6-2.7 (1H, m), 3 , 1-3.3 (1H, m), 3.7-4.5 (16H, m), 4.7-5.4 (11H, m), 5.51 (1H, d, J = 5, 6Hz), 6.7-7.0 (3H, m), 7.0-7.6 (7H, m), 7.74 (1H, d, J = 8.6Hz), 8.0-8, 4 (5H, m), 8.7-8.8 139 (1H, m), 8.84 (1H, s) FAB MASS: m / z = 1301 (M + + Na).

Elemental Analysis calculated for C 55 H 71 N 10 O 22 SNa-6H 2 O C 47.62, H 6.03, N 10.01 Found: C 47.65, H 6.03, N 10.03

Example 16 IR (Nujol): 3353, 1668, 1627, 1540, 1515, 1500 cm -1 NMR (DMSO-d 6, δ): 0.80-1.00 (6H, m), 1.06 (3H, d) , J = 5.9Hz), 1.20-1.53 (4H, m), 1.60-1.95 (5H, m), 2.00-2.65 (8H, m), .2, 80 (2H, t, J = 7.5Hz), 3.05-3.45 (1H, m), 3.50-3.85 (2H, m), 3.90-4.48 (11H, m) ), 4.65-5.38 (11H, m), 5.47 (1H, d, J = 6.0Hz), 6.65-6.90 (2H, m), 6.90-7.10 (2H, m), 7.10-7.65 (11H, m), 7.90-8.25 (2H, m), 8.30 (1H, d, J = 7.8Hz), 8.84 (1 H, s) FAB MASS: m / z = 1275.3 (M + + Na)

Elemental Analysis calculated for C CssHaNNgCC SNaa ^ I I ^O requires C, 50.53; H, 6.09; N, 8.57 Found: C, 50.48; H, 6.39; N, 8.57.

Example 17 IR (Nujol): 3351, 1656, 1623, 1538, 1515 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.96 (3H, d) , J = 6.7Hz), 1.08 (3H, d, J = 5.8Hz), 1.15-1.40 (8H, m), 1.50-2.00 (5H, m), 2 , 10-2.48: (4H, m), 2.52-2.70 (2H, m), 3.05-3.28 (1H, m), 3.60-4.50 (13H, m) ), 4.70-5.20 (9H, m), 5.25 (1H, d, J = 4.6Hz), 5.52 (1H, d, J = 6.0Hz), 6.68-6 , 92 (4H, m), 7.04 (1H, d, J = 1.0Hz), 7.22-7.50 (5H, m), 7.55-7.82 (7H, m), 8.14 (1H, d, J = 8.4Hz), 8.31 (1H, d, J = 8.4Hz), 8.54 (1H, d, J = 7.7Hz), 8.84 (1H, s): 1. FAB MASS: m / z = 1285 (M + + Na)

Example 18; IR (Nujol): 3351, 1668, 1627, 1540, 1515 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.8Hz), 0.96 (3H, d, J = 6.7Hz, 1.06 ^ (3H, d, J = 5.8Hz), 1.17-1.48 (4H, m), 1.50-1.95 (5H, m) , 2.05 - 2.70 (8H, m), 2.70 - 2.95 (2H, m), 3.05 - 3.30 (1H, m), 3.60 - 3.90 (2H, m), 3.90-4.50 (11H, m), 4.65-5.10 (9H, m), 5.15 (1H, d, J = 3.2Hz), 5.23 (1H, d, J = 4.2Hz, 5.48 (1H, d, J = 6.0Hz), 6.67-6.90 (3H, m), 7.03 (1H, d, J = 1.5Hz) ), 7.15-7.80 (11H, m), 8.00-8.20 (2H, m), 8.29 (1H, d, J = 7.8Hz), 8.84 (1H , s) FAB MASS: m / z = 1259 (M + + Na)

Elemental Analysis calculated for C CssH ^ NeNCClSSNa öO öO OO requires C 50.30, H 6.52, N 8.53 Found: C 50.42, H 6.50, N 8.45.

Example 19 140 IR (Nujol): 3351, 1668, 1652, 1623, 1540 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz), 0.96 (3H, d, J = 6.7Hz), 1.07 (3H, d, J = 6.0Hz), 1.25-1.45 (4H, m), 1.50-2.00 (5H, m), 2.05-2.48 (4H, m), 2.50-2.75 (2H, m), 3.60-4.50 (13H, m), 4.68-5.25 (10H, m) ), 5.27 (1H, d, J = 4.5Hz), 5.53 (1H, d, J = 6.0Hz), 6.67-6.98 (4H, m), 7.05 (1H , d, J = 1.0Hz), 7.22-7.58 (5H, m), 7.58-7.90 (7H, m), 8.16 (1H, d, J = 9.0Hz) , 8.34 (1H, d, J = 8.4Hz), 8.57 (1H, d, J = 7.7Hz), 8.85 (1H, s) FAB MASS: m / z = 1258 (M ++ Na)

Elemental Analysis calculated for C CssbibiNNNCg ^SSNa-S ^ ^O requires C, 49.84, H, 6.15, N, 8.45 Found: C, 49.77, H, 6.27, N, 8.39.

Example 20 IR (Nujol): 3353, 1670, 1629, 1540, 1508 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.5Hz), 0.97 (3H, d) , J = 6.8Hz), 1.04 (3H, d, J = 5.9Hz), 1.20-1.58 (8H, m), 1.60-1.96 (5H, m), 2 , 08-2.60 (6H, m), 2.70-3.00 (2H, m), 3.00-3.40 (1H, m), 3.60-3.85 (2H, m) , 3.85-4.50 (13H, m), 4.50-5.60 (12H, m), 6.65-6.90 (3H, m), 7.00-7.15: (3H , m), 7.18-7.50 (4H, m), 7.59 (1H, s), 7.62-7.78 (2H, m), 7.95-8.20 (2H, m) ), 8.30 (1H, d, J = 7.7Hz), 8.83 (1H, s) F /, FAB MASS: m / z = 1277 (M + + Na).

Elemental Analysis calculated for 055-75Ν802223Ν3 · 4Η20 C 49.77, H 6.30, N 8.44; Found: C, 49.67; H, 6.31; N, 8.40

Example 21; IR (Nujol): 3351, 1654, 1623, 1538, 1515 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz), 0.97 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5.9Hz), 1.20-1.58 (8H, m), 1.66-1.95 (5H, m), 2.10 -2.60 (4H, m), 3.09-3.30 (1H, m), 3.58-4.60 (15H, m), 4.69-5.20 (10H, m), ' 5.24 (1H, d, J = 4.5Hz), 5.51 (1H, d, J = 6.0Hz), 6.68-6.95 (4H, m), 7.04 (1H, d, J = 1.0Hz), 7.10-7.73 (7H, m), 7.73-7.90 (2H, m), 7.98, 1H (d, J). 1.9Hz), 8.10 (1H, d, J = 8.4Hz), 8.32 (1H, d, J = 8.4Hz), 8.50: (1H, d, J = 7.7Hz) ), 8.84 (1H, s) FAB MASS: m / z = 1275 (M + + Na)

Elemental Analysis calculated for C55H73N8022SNa-5H20

Example 22 C 50.38, H 6.38, N 8.55 Found: C 49.98, H 6.37, N 8.41 141 IR (KBr): 3340, 2931, 1664, 1627, 1531, 1444, 1278, 1047 cm -1 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6.6Hz), 0.96 (3H, d, J = 6.8Hz), 1.08 (3H) , d, J = 5.9Hz), 1.2-1.4 (6H, m), 1.5-1.7 (2H, m), 1.7-2.1 (3H, m), 2 , 2-2.4 (3H, m), 2.6-2.7 (3H, m), 3.1-3.2 (1H, m), 3.7-4.6 (13H, m) , 4.78 (1H, d, J = 6.0Hz), 4.8-5.1 (1H, m), 5.09 (1H, d, J = 5.6Hz), 5.16 (1H, d, J = 3.2Hz, 5.24 (1H, d, J = 4.4Hz), 5.52 (1H, d, J = 6.0Hz), 6.73 (1H, d, J = 8 , 2Hz), 6.83 (2H, d, J = 8.3Hz), 7.05 (1H, s), 7.3-7.5 (5H, m), 7.65 (2H, d, J = 8.2Hz), 7.74 (2H, d, J = 8.4Hz), 7.98 (2H, d, J = 8.4Hz), 8.11 (1H, d, J = 8.4Hz) , 8.31 (1H, d, J = 8.4Hz), 8.79 (1H, d, J = 7.7Hz), 8.84 (1H, s) FAB MASS: m / z = 1245 (M ++ Na)

Elemental Analysis calculated for C54H71N802iSNa, 4H2O C 50.07, H 6.15, N 8.65 Found: C 50.26, H 6.44, N 8.67

Example 23 NMR (DMSO-d 6, δ): 0.91 (3H, t, J = 6.7Hz), 0.96 (3H, d, J = 6.8Hz), 1.05: '(3H, d, J = 5.6Hz), 1.2-1.5 (6H, m), 1.6-2.1 (5H, m), 2.1-2.7 (4H, m) ,; :; 3.0-3.5 (9H, m), 3.6-4.5 (15H, m), 4.6-5.6 (11H, m), 6.73 (1H, d, J = 8 , 2Hz), 6.8-6.9 (4H, m), 6.95 (2H, d, J = 8.6Hz), 7.02 (2H, d, J = 9.2Hz), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.82 (2H, d, J = 8.6Hz), 8.06 1 '(1H, d, J = 8Hz) ), 8.25 (1H, d, J = 6.7Hz), 8.43 (1H, d, J = 6.7Hz), 8.85 (in, s) IR (KBr): 3350, 1668, 1629 , 1510 cm -1 FAB MASS: m / z = 1345 (M + Na)

Elemental Analysis calculated for C 8 H 8 N 8 O 4 C 6 SN 4 H 2 O 3 P 2 O: C 48.67, H 6.41, N 9.78 Found: C 48.80, H 6.46, N 9.82 1. IR (KBr): 3350, 1668, 1631, 1047 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5 , 7Hz), 1.2-1.6 (10H, m), 1.6-2.4 (8H, m), 2.5-2.7 (1H, m), 3.18 (1H, m) ), 3.21 (3H, s), 3.29 (2H, t, J = 6.4Hz), 3.6-3.83 (2H, m), 3.83-4.6 (13H, m) ), 142 4.7-5.4 (11H, m), 5.51 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.2Hz), 6.83 ( 1H, d, J = 8.2Hz), 6.85 (1H, s), 7.04 (2H, d, J = 8.4Hz), 7.06 (1H, s), 7.31 (1H, s), 7.2-7.5 (2H, m), 7.67 (2H, d, J = 8.4Hz), 7.71 (2H, d, J = 8.4Hz), 7.96 ( 2H, d, J = 8.4Hz), 8.06 (1H, d, J = 6.7Hz), 8.25 (1H, d, J = 6.7Hz), 8.74 (1H, d, J = 6) , 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1319 (M + Na)

Elemental Analysis calculated for C57H77N8023SNa'4H2O C 49, 99, H 6.26, N 8.18 Found: C 49.74, H 6.27, N 8.06

By-product IR (KBr): 3350, 1668, 1631 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5, 7Hz), 1.2-1.6 (6H, m), 1.6-2.1 (7H, m), 2.1-2.5 (3H, m), 2.5-2.7 ( 1H, m), 3.18 (1H, m), 3.6-3.8 (2H, m), 3.8-4.6 (13H, m), 4.6-5.2 (12H, m), 5.26 (1H, d, J = 4.6Hz), 5.53 (1H, d, J = 5.8Hz), 5.6-6.0 (1H, m), 6.73 ( 1H, d, J = 8.2Hz), 6.83 (1H, d, J = 8.3Hz), 6.85 (1H, s), 7.04 (2H, d, J = 8.5Hz), 7.06 (1H, s), 7.30 (1H, s), 7.2-7.5 (2H, m), 7.68 (2H, d, J = 8.5Hz), 7.72 ( 2H, d, J = 8.5Hz), 7.96 (2H, d, J = 8.5Hz), 8.06 (1H, d, J = 8Hz), 8.25 (1H, d, J = 6) , 7Hz), 8.74 (1H, d, J = 6.7Hz), 8.85 (1H, s) FAB MASS: m / z = 1287 (M + Na).

Elemental Analysis calculated for C56H73N8NaO22S-7H2O C 48.34, H 6.30, N 8.05 Found: C 48.19, H 6.19, N 7.99 Example 25: v, IR (KBr): 3350 , 2935, 2873, 1668, 1629, 1538, 1506, 1438, 1257, 1049 cm -1 NMR (DMSO-d 6, δ): 0.9-1.0 (6H, m), 1.08 (3H) , d, J = 5.7Hz), 1.2-1.6; (4H, m), 1.6-2.0 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3 , 2: 'i'; (1H, m), 3.6-4.6 (15H, m), 4.7-5.2 (10H, m), 5.26 (1H, d J = 4.5Hz), 5.55 ( 1H, d, J = 5.9Hz), 6.7-6.9 (3H, m), 7.0-7.6 (7H, m), 7.85 (2H, d, J = 8.6Hz) ), 7.9-8.2 (4H, m), 8.26 (1H, d, J = 7.7Hz), 8.8-9.0 (2H, m); FAB MASS: m / z = 1314.3 (M + Na) +: Elemental analysis calculated for C CseyoNNggg ^ ^ NaSS ^ t O: C, 47.42; H, 5.97; N, 8.89. C, 47.33; H, 5.85; N, 8.73; Example 26

To a solution of the starting compound (1 g) and succinimido; 4- (4-Octyloxyphenyl) piperazine-1-carboxylate (0.45 g) in N, N-dimethylformamide (10 ml) was added 4-dimethylaminopyridine (0.141 g) and stirred for 5 days at 50 ° C. The reaction mixture was made 143 powdered with ethyl acetate. The precipitate was collected by filtration and dried under reduced pressure. The powder was dissolved in water and column chromatography eluting with ion exchange resin (DOWEX-50WX4) with water. The fractions containing the target compound were combined and column chromatographed with ODS (YMC-gelODS-AM'S-50) eluting with 50% aqueous acetonitrile. The fractions containing the target compound were combined and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give the crude target compound (23). The powder containing the crude target compound (23) was purified by preparative HPLC using C18 μ Bondapak resin (Waters Associates, Inc.) eluted with a solvent system containing (acetonitrile pH 3 phosphate buffer = 40:60) at a flow rate of 80 mL. / minute using a Shimadzu LC-8A pump. The column was monitored with a UV detector at 240 µm. The fractions containing the target compound were combined and evaporated under reduced pressure to remove acetonitrile. The residue was subjected to column chromatography on ion exchange resin (DOWEX-50WX4) eluting with water. The fractions containing the target compound were combined and column chromatographed with ODS (YMC-gelODS-AM-S-50) eluting with 50% aqueous acetonitrile. The fractions containing the target compound were combined and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give the target compound (23) (60 mg).

IR (KBr): 3347, 1629, 1511, 1245 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.95 (3H, d, J = 6 , 8Hz), 1.06 (3H, d, J = 5.9Hz), 1.2-1.5 (10H, m), 1.55-1.92 (5H, m), 2.0-2 , 65 (4H, m), 2.8-3.05 (5H, m), 3.2-4.47 (17H, m), 4.6-5.6 (12H, m), 6, 6-7.0: 7: (7H, m), 7.03 (1H, s), 7.2-7.5 (3H, m), 7.9-8.3 (3H, m), δ , 84 (1H, 1H, V, s) FAB MASS: m / z = 1297 (M + + Na).

Elemental Analysis calculated for C Cs ^HNNNOC · · · · · · · · · · · · · ·CHCHsN · O · OCHsCN: C, 47.22; H, 6.65; N, 10.82: 7; Found: C, 47.58;

Example 27

To a suspension of 1-hydroxybenzotriazole (0.53 g) and 2- (4-; octyloxyphenoxy) acetic acid (1 g) in dichloromethane (30 mL) was added 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide: 1 imide dihydrochloride (WSCD-HCl) (0.886 g) was stirred for 3 hours at ambient temperature. The reaction mixture was added to water. The organic layer was separated and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 1- [2- (4-octyloxy-phenoxy) -acetyl] -benzotriazole-3-oxide (892 mg). To a solution of the starting compound 144 (1.79 g) and 1- [2- (4-octyloxy-phenoxy) -acetyl] -benziazole-3-oxide (892 mg) in N, N-dimethylformamide (18 ml) was added 4- (N). , N-dimethylamino) pyridine (0.297 g) and stirred for 12 hours at ambient temperature. The reaction mixture was made powdered with ethyl acetate. The precipitate was collected by filtration and dried under reduced pressure. The powder was added to water and ion exchange column chromatography on DOWEX-50WX4 and eluted with water. The fractions containing the target compound were combined and column chromatographed with ODS (YMC-gelODS-AM-S-O) and eluted with 50% aqueous methanol. The fractions containing the target compound were combined and evaporated under reduced pressure to remove methanol. The residue was lyophilized to give the target compound (24) (1.75 g).

IR (KBr): 3350, 1666, 1629, 1228 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.9Hz), 0.95 (3H, d, J = 6 , 7Hz), 1.04 (3H, d, J = 5.7Hz), 1.15-1.5 (10H, m), 1.55-2.0 (5H, m), 2.05-2 , Δ (4H, m), 3.16 (1H, m), 3.72 (2H, m), 3.88 (3H, t, J = 6.3Hz), 4.41 (2H, s), 3.93-4.6 (1H, m), 4.69-5.25 (10H, m), 5.28 (1H, d, J = 4.3Hz), 5.57 (1H, d, J) = 5.7Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (5H, m), 7.04 (1H, s), 7.09 (1H, s) ), 7.3-7.4 (2H, m), 7.92-8.17 (2H, m), 8.29 (1H, d, J = 7.5Hz), 8.84 (1H, s) ) FAB MASS: m / z = 1243 (M + + Na)

Elemental Analysis calculated for C51H73N8023SNa-4H20 C 47.36, H 6.31, N 8.66.11 Found: C 47.22, H 6.44, N 8.37.

The target compounds (28) to (31) were obtained according to Example 27.

Example 28 IR (KBr): 3350, 2933, 1664, 1628, 1446, 1205, 1045 cm -1 NMR (DMSO-d 6, δ): 0.8-1.1 (9H, m), 1.2-2 , 0 (19H, m), 2.1-2.3 (3H, m), 3.6-3.8 (4H, m), 3.9-4.4 (13H, m), 4.6 -5.0 (8H, m), 5.07 (1H, d, J = 5.6Hz), 5.14 (1H, d, J = 3.2Hz), 5.23 (1H, d, J = 4.3Hz), 5.46 (1H, d, J: 6.7Hz), 6.7-6.9 (3H, m), 7.04 (1H, s), 7, 2-7.5 (6H, m), 7.8-8.0 (3H, m), 8.05 (1H, d, J = 8.4Hz), 8.2-8.4 (2H, m) ), 8.83 (1H, s) 'N': FAB MASS: m / z = 1360 (M + + Na)

Elemental Analysis calculated for C59H90N9023SNa-6H2O C 48.99, H 6, 41, N 8.72.1; . Found: C 48, 92, H 6.37, N 8.64

Example 29 145 IR (KBr): 3350, 2927, 1668, 1627, 1535, 1515, 1452, 1440, 1286, 1045 cm -1 NMR (DMSO-d 6, δ): 0.83 (3H, t, J = 6 , 7Hz), 0.95 (3H, d, J = 6.7Hz), 1.07 (3H, d, J = 5.9Hz), 1.2-1.4 (12H, m), 1.6 -2.0 (5H, m), 2.1-2.4 (3H, m), 2.6 (1H, m), 2.82 (2H, t, J = 7.4Hz), 3.1 -3.2 (1H, m), 3.6-4.5 (13H, m), 4.7-5.2 (11H, m), 5.4-5.6 (1H, m), 6 , 72 (1H, d, J = 8.2Hz), 6.82 (2H, d, J = 8.1Hz), 7.03 (1H, s), 7.2-7.4 (3H, m) , 7.47 (1H, d, J = 8.5Hz), 7.69 (1H, d, J = 8.5Hz), 8.1-8.2 (2H, m), 8.23 (1H, d, J = 8.4Hz), 8.62 (1H, d, J = 7.8Hz), 8.83 (1H, s) FAB MASS: m / z = 1251 (M + + Na)

Elemental Analysis calculated for C52H73N10O2SNa-5H2O C 47.34, H 6.34, N 10.61 Found: C 47.30, H 6.45, N 10.45

Example 30 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6.8Hz), 0.96 (3H, t, J = 6.7Hz), 1.05 (3H, t, J = 5.8Hz), 1.2-1.5 (10H, m), 1.6-2.0 (5H, m), 2.2-2.4 (3H, m), 2.5-2 , 6 (1H, m), 3.1-3.2 (1H, m), 3.7-4.5 (15H, m), 4.7-5.0 (8H, m), 5.10 (1H, d, J = 5.6Hz), 5.17 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.52 (1H, d, J = 5.8Hz) 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (3H, m), 7.04 (1H, s), 7.2-7.4 (3H, m), 8.0-8.3 (3H, m), 8.68 (1H, d, J = 2.3Hz), 8.7-8.8 (1H, m), 8.85 (1 H, m) FAB MASS: m / z = 1214 (M + + Na) 11 Elemental analysis calculated for C 24 H 20 N 4 O 4 SNa 2 H 2 O 4 requires C 46.55, H 6.22, N 9.97, ' V, Found: C, 46.29; H, 6.18; N, 9.71

Example 31 IR (Nujol): 3342, 2210, 1668, 1623 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.7Hz), 0.97 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 6.7Hz), 1.20-1, 60 (8H, m), 1.60-2.00 (5H, m), 2.05 -2.50; (4H, m), 3.05-3.30 (1H, m), 3.60-4.60 (15H, m), 4.65-5.18 (10H, m), 5.24 (1H, d, J = 4.5Hz), 5.58 (1H, d, J = 6.0Hz), 6.68-7.10 (4H, m), 7.15-7.65 (5H, m), 7.80-8.30 (6H, m), 8.84 (1H, s), 9.18 (1H, d, J = 7.7Hz) FAB MASS: m / z = 1273.5 (M + + Na) 1: Example 32

To a solution of 6-heptyloxy-2-naphthoic acid (0.358 g) and triethylamine (0.174 ml) in N, N-dimethylformamide 146 (10 ml) was added diphenylphosphoryl azide (0.4 ml) and stirred for 1 hour at ambient temperature. The reaction mixture was then stirred for one hour at 100 ° C. After cooling, the reaction mixture (1 g) and 4- (N, N-dimethylamino) pyridine (0.140 g) were added to the reaction mixture and stirred for 10 hours at ambient temperature. The reaction mixture was made powdered with ethyl acetate. The precipitate was collected by filtration and dried under reduced pressure. The powder was dissolved in water and column chromatographed with ion exchange resin (DOWEX-50WX4) eluting with water. The fractions containing the target compound were combined and column chromatographed with ODS (YMC-gelODS-AM'S-SO) eluting with 50% aqueous acetonitrile. The fractions containing the target compound were combined and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give the target compound (29) (0.832 g).

IR (KBr): 3350, 1664, 1629, 1546, 1240 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.6Hz), 0.97 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5.9Hz), 1.2-1.55 (8H, m), 1.55-2.0 (5H, m), 2.1 -2.5 (4H, m), 3.18 (1H, m), 3.6-3.8 (3H, m), 3.9-4.5 (13H, m), 4.7-4 , 95 (3H, m), 5.0-5.3 (7H, m), 5.59 (1H, d, J = 5.8Hz), 6.52 (1H, d, J = 8.1Hz) , 6.73 (1H, d, J = 8.2Hz), 6.83 (1H, d, J = 8.2Hz), 6.90 (1H, s), 7.0-7.15 (3H, m) , 7.20 (1H, s), 7.27-7.4 (3H, m), 7.6-7.7 (2H, m), 7.87 (1H, s), 7.95-8 , 2 (2H, m), 8.69 (1H, s), 8.85 (1H, s) FAB-MS: m / z = 1264 (M + + Na).

Elemental Analysis calculated for C 5 H 6 N 8 O 4 SNa-St 2 O; (C 47.78, H 6.20, N 9.46 found: C 47.65, H 6.42, N 9.34

The target compound (33) was obtained according to Example 32.

Example 33 IR (KBr): 3350, 1666, 1629, 1537, 1240 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz), 0.97 (3H, d) , J = 6.7Hz), 1.09 (3H, d, J = 5.8Hz), 1.2-1.55 (8H, m), 1.55-2.0 (5H, m), 2 , 07-2.6 (4H, "m), 3.18 (1H, m), 3.6-3.85 (3H, m), 3.9-4.5 (13H, m), 4 , 7-4.98 (3H, :: m), 5.0-5.3 (7H, m), 5.57 (1H, d, J = 5.9Hz), 6.50 (1H, d, J = 8.1Hz), 6.73 (1H, d, J = 8.2Hz), 6.82 (1H, dd, J = 8.2 and 1.7Hz), 6.87 (1H, s), ι · 6.97 (2H, d, J = 8.8Hz), 7.05 (1H, d, J = 1.7Hz), 7.10 (1H, s), 7.23-7.43 ( 2H, m), 7.38 (2H, d, J = 8.8Hz), 7.50 (2H, d, J = 8.8Hz), 7.52 L; (2H, d, J = 8.8Hz) ), 8.0-8.15 (2H, m), 8.65 (1H, s), 8.84 (1H, s) FAB MASS: m / z = 1290 (M + + Na). Elemental Analysis calculated for C CssH ^ NN NC ^ SNNa ^ i iO O C 47.38, H 6.36, N 9.04 Found: C 47.67, H 6.53, N 9.03

Example 34 147

A solution of the starting compound (2.45 g), 3- [4- (4-pentylphenyl) phenyl] propiolic acid (0.90 g), 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide hydrochloride ( WSCD-HCl) (0.59 g) and triethylamine (0.43 ml) in N, N-dimethylformamide (50 ml) were stirred for 15 hours at ambient temperature. The reaction mixture was diluted with ethyl acetate and the resulting precipitate was collected by filtration and washed alternately with ethyl acetate and diisopropyl ether and dried under reduced pressure. The powder was dissolved in water and column chromatographed with ion exchange resin (DOWEX-50WX4 (Na form, 50 mL)) eluting with water. The fractions containing the target compound were combined and reverse phase chromatographed with ODS (YMC-gelODS-AM'S-50, 50 mL) eluting (water: acetonitrile = 10: 0-7: 3, v / v). The fractions containing the target compound were combined and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give the target compound (31) (1.53 g).

IR (Nujol): 3351, 2212, 1668, 1627 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.5Hz), 0.96 (3H, d, J = 6 , 7Hz), 1.08 (3H, d, J = 5.8Hz), 1.20-1.50 (4H, m), 1.50-2.00 (5H, m), 2.03-2 , 55 (4H, m), 2.62 (2H, t, J = 7.5Hz), 3.17 (1H, t, J = 8.4Hz), 3.55-4.57 (15H, m) , 4.65-5.13 (9H, m), 5.16 (1H, d, J = 3.2Hz), 5.24 (1H, d, J = 4.5Hz), 5.58 (1H, d, J = 5.8Hz), 6.67-6.90 (3H, m), 6.93-7.10 (2H, m), 7.15-7.50 (4H, m), 7, 50-7.90 (6H, m), 8.06 (1H, d, J = 7.4Hz), 8.15 (1H, d, J = 7.7Hz), 8.84 (1H, s), 9.19 (1H, d, J = 7, 1Hz) δ 1.1 FAB MASS: m / z = 1255 (M + + Na): 1; Elemental analysis calculated for: 055 6169 H8θ2ΐ3Ν3 · 4Η20: C 50, 61, H 5 , 95, N 8.58 Found: C 50.47, H 6.00, N 8.54; Example 35

To a suspension of 1-hydroxybenzotriazole (501 mg) and 4- (4-heptylphenyl) benzoic acid (1 g) in dichloromethane (30 mL) was added 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide. imide hydrochloride (WSCD-HCl) (839 mg) and stirred for 3 hours at ambient temperature The reaction mixture was added to water The organic layer '·· <' was separated and dried over magnesium sulfate The magnesium sulfate was filtered off and the filtrate was evaporated under reduced pressure [4- (4-Heptylphenyl) -benzoyl] -benzotriazole 3- "·" Oxide To a solution of the starting compound (2.49 g) and 1- [4- (4 - ((trans) Heptylphenyl) benzoyl] benzotriazole-3 oxide in N, N-dimethylformamide (25 mL) was added 4- (N, N-dimethylamino) pyridine (381 mg) and stirred for 12 hours at ambient temperature, The reaction mixture was powdered with ethyl acetate The precipitate was collected by filtration and dried under reduced pressure The residue was dissolved in water and column chromatography on ion exchange resin (DOWEX-50WX4) eluting with water. The fraction containing the target compound was combined and column chromatographed with ODS (YMC-gelODS-AM-S-O) eluting with 30% aqueous acetonitrile. The fractions containing the target compound were combined and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give the target compound (32) (1.99 g).

IR (Nujol): 3350, 2852, 1749, 1621, 1457, 1376, 1045 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), 0.96 (3H) , d, J = 6.7Hz), 1.08 (3H, d, J = 5.9Hz), 1.5-1.7 (2H, m), 1.7-2.2 (3H, m) , 2.2-2.5 (3H, m), 2.6-2.8 (3H, m), 3.1-3.2 (1H, m), 3.7-4.6 (13H, m), 4.7-5.2 (8H, m), 5.12 (1H, d, J = 5.5Hz), 5.18 (1H, d, J = 2.9Hz), 5.27 ( 1H, d, J = 4.4Hz), 5.54 (1H, d, J = 5.8Hz), 6.7-6.9 (3H, m), 7.05 (1H, s), 7, 2-7.4 (5H, m), 7.65 (2H, d, J = 8.0Hz), 7.74 (2H, d, J = 8.3Hz), 7.98 (2H, d, J) = 8.3Hz), 8.11 (1H, d, J = 8.7Hz), 8.28 (1H, d, J = 8.4Hz), 8.78 (1H, d, J = 7.3Hz) , 8.85 (1H, s) FAB MASS: m / z = 1259 (M + + Na)

Elemental Analysis calculated for C55H73N802iSNa-5H2O C 49.77, H 6.30, N 8.44 Found: C 49.98, H 6.44, N 8.41 The conjugate compounds (36) to (107) were obtained according to Example 1.

'' 'Example 36: V, IR (KBr): 3350, 1675.8, 1629.6, 1515.8 cm -1 NMR (DMSO-d 6, δ): 0.86 (6H, d, J = 6, 6Hz), 0.96 (3H, d, J = 6.6Hz), 1.06 ': (3H, d, J = 5.7Hz), 1.1-1.3 (2H, m), 1, 4-2.0 (6H, m), 2.0-2.7 (4H, m), I 3.1-3.5 (9H, m), 3.66 (2H, t, J = 7, 3Hz), 3.6-4.5 (13H, m), 4.7-5.6 dj '; (12H, m), 6.73 (1H, d, J = 8.3Hz), 6.82 (1H, d, J = 8.3Hz), 6.8-6.9 (1H, m), , 02 (2H, d, J = 9.0Hz), 7.04 (1H, s), 7.11 (2H, d, J = 9.0Hz), 7.2-7.6 (3H, m) , 7.50 (2H, d, J = 9.0Hz), 7.82 (2H, d, J = 9.0Hz), 8.1 (1H, d, J = 8.5Hz), 8, 28 (1H, d, J = 8.5Hz), 8.33 (1H, s), 8.45 (1H, d, J = 7.0Hz), 8.8 (1H, s) FAB MASS: m / z = 1412 (M + Na)

Elemental Analysis calculated for C60H8N13022SNa-9H2O requires C 46.42, H 6.36, N 11.73 Found: C 46.64, H 6.43, N 11.62.1 Example 37 IR (KBr) : 3350, 1668.1, 1629.6, 1268.9 cm-1 149 NMR (DMSO-d6, δ): 0.85 (3H, t, J = 6.6Hz), 0.96 (3H, d, J = 6.7Hz), 1.07 (3H, d, J = 5.9Hz), 1.2-1.4 (10H, m), 1.4-2.0 (5H, m), 2, 0-2.5 (4H, m), 2.61 (2H, t, J = 7.2Hz), 3.1-3.3 (1H, m), 3.6-4.5 (13H, m) ), 4.40 (2H, s), 4.6-5.3 (11H, m), 5.60 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8) , 2Hz), 6.82 (1H, d, J = 8.2Hz), 6.6-6.9 (1H, m), 7.04 (1H, s), 7.0-7.1 (1H , m), 7.32 (2H, d, J = 8.5Hz), 7.2-7.5 (2H, m), 7.58 (2H, d, J = 8.5Hz), 7.93 (1H, d, J = 7Hz), 8.04 (1H, d, J = 9.4Hz), 8.41 (IR, s), 8.44 (1H, d, J = 9.4Hz), δ , 84 (1H, s) FAB MASS: m / z = 1294 (M + Na).

Elemental Analysis calculated for C53H74N11022SNa -7H2O C 45.52, H 6.34, N 11.02 Found: C 45.47, H 6.27, N 10.93

Example 38 Main product IR (KBr): 3349.7, 1670.1, 1627.6, 1508.1 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.6Hz), 1.06 (3H, d, J = 5.7Hz), 1.2-1.6 (8H, m), 1.6-2.1 (5H, m), 2.1-2.7 (4H, m) ), 3.0-3.2 (5H, m), 3.21 (3H, s), 3.30 (2H, t, J = 6.5Hz), 3.3-3.5 (4H, m) ), 3.6-4.5 (15H, m), 4.7-5.3 (11H, m), 5.49 (1H, d, J = 5.9Hz), 6.73 (1H, d) , J = 8.3Hz), 6.8-6.9 (4H, m), 6.95 (2H, d, J = 9.2Hz), 7.01 (2H, d, J = 8.5Hz) , 7.04 (1H, s), 7.20 (1H, s), 7.2-7.5 (2H, m), 7.81 (2H, d, J = 8.5Hz), 8.09 (1H, d, J = 8.7Hz), 8.28 (1H, d, J = 8.7Hz), 8.45 (1H, d, J = 6.7Hz), 8.84 (1H, s) : FAB MASS: m / z = 1389 (M + Na) • Elemental Analysis calculated for C 50 H 83 N 10 O 23 SNa-8H 2 O: C, 47.68, H 6.60, N 9.27 Found: C 47.83, H 6.72, N, 9.27; By-product IR (KBr): 3338.2, 1646.9, 1511/9 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.06 (3H) , d, J = 5.7Hz), 1.3-1.6 (4H, m), 1.6-2.7 (11H, m), 3.0-3.2 (5H,, m), 3, 3-3.5 (4H, m), 3.6-4.5 (15H, m), 4.7-5.3 (13H, m), 5.48 (1H, d, J = 5, 9Hz), 5.7-6.0 (1H, m), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (4H, m), 6.94 (2H, d, J = 9.3Hz), 7.01 (2H, d, J = 8.6Hz), 7.04 (1H, s), 7.2-7.5 (3H, m), 7, 81 (2H, d, J = 8.6Hz), 8.06 (1H, d, J = 8.7Hz), 8.25 (1H, d, J = 8.7Hz), 8.42t ": ( 1H, d, J = 6.7Hz), 8.84 (1H, s) FAB MASS: m / z = 1357 (M + Na) 1. Elemental analysis calculated for C IC 47.32, H 6, 53, N 9, 35 Found: C, 47.08, H, 6.66, N, 9.25.

Example 39 150 IR (KBr): 3350, 1670.1, 1631.5, 1510.0, 1234.2 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz) ), 0.96 (3H, d, J = 6.7Hz), 1.06 (3H, d, J = 5.6Hz), 1.2-1.5 (8H, m), 1.6-2 , 1 (5H, m), 2.1-2.7 (4H, m), 3.0-3.3 (5H, m), 3.3-3.5 (4H, m), 3.6-3 , Δ (2H, m), 3.88 (2H, d, J = 6.4Hz), 3.8-4.5 (11H, m), 4.7-5.1 (8H, m), δ , 10 (1H, d, J = 5.6Hz), 5.16 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.5Hz), 5.48 (1H, d, J = 5.9Hz, 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (4H, m), 6.94 (2H, d, J = 9.3Hz) ), 7.01 (2H, d, J = 8.7Hz), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.81 (2H, d, J = 8 , 7Hz), 8.06 (1H, d, J = 6.7Hz), 8.25 (1H, d, J = 6.7Hz), 8.43 (1H, d, J = 6.7Hz), 8.85 (1 H, s) FAB MASS: m / z = 1359 (M + Na)

Elemental Analysis calculated for C59H8N10O22SNa'5H2O C 49.64, H 6.43, N 9.81 Found: C 49.49, H 6.54, N 9.72.

Example 40 IR (KBr): 3355.5, 1670.1, 1627.6, 1510.0 1236.1 cm -1 NMR (DMSO-d 6, δ): 0.89 (6H, d, J = 6.5Hz) ), 0.96 (3H, d, J = 6.7Hz), 1.05 (3H, d, J = 5.7Hz), 1.2-1.4 (2H, m), 1.5-2 , 1 (6H, m), 2.1-2.7 (4H, m), 3.0-3.6 (9H, m), 3.6-4.5 (15H, m), 4.5-5 , 4 (12H, m), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (4H, m), 6.96 (2H, d, J = 9.6Hz) , 7.02 (2H, d, J = 8.7Hz), 7.05 (1H, s), 7.2-7.5 (3H, m), 7.82 (2H, d, J = 8, 7Hz), 8.08: (1H, d, J = 6.7Hz), 8.27 (1H, d, J = 6.7Hz), 8.46 (1H, d, J = 6.7Hz), 8.85 (1H, s) F. ', FAB MASS: m / z = 1345 (M + Na), Elemental analysis calculated for C58H79N10O22SNa'8H2O C 47.47, H 6.52, N 9.54; C, 47.47; H, 6.54; N, 9.51

Example 41: IR (KBr): 3347.8, 1668.1, 1629.6, 1510.0, 1234.2 cm -1 NMR (DMSO-d 6, δ): 0.89 (3H, t, J = 7 , 0Hz), 0.96 (3H, d, J = 6.7Hz), 1.05 (3H, d, J = 5.8Hz), 1.2-1.5 (4H, m), 1.6 -2.1 (5H, m), 2.1-2.7 (4H, m), 3.0-3.6 (9H, m), 3.6-3.8 (2H, m), 3.8 -4.5 (13H, m), 4.7-5.6 (12H, 11.1m), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (4H , m), 6.96 (2H, d, J = 8.7Hz), 7.02 (2H, d, J = 9.0Hz), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.82 (2H, d, J = 8.7Hz), 8.07 (1H, d, J = 8Hz), 8.27 (1H, d, J = 6.7Hz), δ 8.45 (1H, d, J = 6.7Hz), 8.85 (1H, s) FAB MASS: m / z = 1331 (M + Na)

Elemental Analysis calculated for C57H77N10O22SNa-6H2O C 48.30, H 6.33, N 9, 88 Found: C 48.20, H 6.58, N 10.03 151

Example 42 Product mixture IR (KBr): 3344, 1670.1, 1631.5 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5.9Hz), 1.2-1.5 (8H, m), 1.6-2.1 (7H, m), 2.1-2.7 (4H, m), 3.1-. 3.3 (1H, m), 3.6-4.5 (15H, m), 4.45 and 4.70 (2H, t, J = 7.1 Hz), 4.6-5.3 (11H, m). ), 5.52 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.2Hz), 6.83 (1H, d, J = 8.2Hz), 6.85 (1H, s), 7.03 (2H, d, J = 8.6Hz), 7.05 (1H, s), 7.2-7.5 (3H, m), 7.68 (2H, d) , J = 8.6Hz), 7.71 (2H, d, J = 8.4Hz), 7.96 (2H, d, J = 8.4Hz), 8.12 (1H, d, J = 8, 5Hz), 8.30 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1357 (M + Na)

Elemental Analysis calculated for C57H75N12022SNa-4H2O C 48.64, H 5.94, N 11.94 Found: C 48.91, H 5.88, N 11.86.

Example 43 IR (KBr): 3350, 1666.2, 1651.5 cm -1 NMR (DMSO-d6, δ): 0.96 (3H, d, J = 6.7Hz), 1.05 (6H, d) , J = 6.3Hz), 1.06 (3H, d, J = 5.7Hz), 1.2-1.6 (10H, m), 1.6-2.1 (7H, m), 2 , 1-2.7 (6H, m), 2.8-3.0 (2H, m), 3.0-3.2 (1H, m), 3.4-3.7 (2H, m) , 3.6-3.8 (2H, 1 "m), 3.8-4.5 (13H, m), 4.7-5.6 (12H, m), 6.73 (1H, d, J = 8.2-Hz), 6.8-7.0 (2H, m), 7.03 (2H, d, J = 8.7Hz), 7.06 (1H, s), 7.2- 7.5 (3H, m), δ, 7.67 (2H, d, J = 8.7Hz), 7.71 (2H, d, J = 8.4Hz), 7.96 (2H, d, J = 8.4Hz), 8.04 (1H, d, J = 8.5Hz), 8.31 (1H, d, J = 8.5Hz), 8.73 (1H, d, J = 7, 0Hz): 8.90 (1H, s); FAB MASS: m / z = 1402 (M + Na)

Example 44 IR (KBr pellet): 3350, 2929, 2856, 1670, 1631, 1510, 1243, 1045 cm -1, 11 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.8Hz), 0.96 (3H, d, J = 6.7Hz), 1.06 (3H, d, J = 5.7Hz), 1.6-2.0 (5H, m), 2, 2-2.5 (5H, m), 2.6-2.7 (1H, m), 3.0-3.3 (5H, m), 3.6-4.5 (19H, m), 4.77 (2H, d, J = 5.9Hz), 4.8-5.1 (6H, m), 5.10 (1H, d, J = 5.6Hz), 5.17 (1H, d , J = 3.1Hz), 5.25 (1H, d, J = 4.5Hz), 5.50 (1H, d, J = 5.8Hz), 6.7-7.0 (8H, m), 7.04 (1H, s), 7.2-7.4 (3H, m), 8.0-8.2 (2H, m), 8.26 (1H, d, J = 8, 0Hz), 8.55 (1H, d, J = 7.3Hz), 8.67 (1H, d, J = 1.2Hz), 8.85 (1H, s) FAB MASS: m / z = 1374 , 3 (M + Na +)

Elemental Analysis calculated for C CS9H821NNO22O22NaS, 5.5H CO requires C, 48.82; H, 6.46; N, 101.61 Found: C, 48.89; H, 6.74; N, 10.50.

Example 45 IR (KBr): 3350, 2935, 1668, 1623, 1538, 1257, 1174, 1047 cm -1 NMR (DMSO-d 6, δ): 0.8-1.1 (6H, m), 1.09 (3H, d, J = 5.7Hz), 1.2-1.6 (6H, m), 1.7-2.1 (5H, m), 2.2-2.4 (3H, m) , 2.5-2.6 (1H, m), 3.6-3.8 (2H, m), 3.8-4.6 (14H, m), 4.8-5.2 (7H, m), 5.18 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.54 (1H, d, J = 5.8Hz), 6, 7-7.5 (9H, m), 7.82 (1H, d, J = 8.5Hz), 7.96 (1H, d, J = 8.7Hz), 8.1-8.4 (5H) , m), 8.8-9.0 (2H, m) FAB MASS: m / z = 1302.6 (M + Na +).

Elemental Analysis calculated for C 55 H 70 N 8 O 2. 23SNa-6H 2 O C 47.58, H 5.95, N 9.08 Found: C 47.46, H 6.04, N 9.05

Example 46 IR (KBr): 3355, 2958, 1670, 1627, 1521, 1247, 1047 cm -1 NMR (DMSO-d 6, δ): 0.9-1.0 (6H, m), 1.08 (3H) , d, J = 5.6Hz), 1.4-1.6 (2H, m), 1.7-2.1 (5H, m), 2.1-2.4 (3H, m), 2 , 5-2.6 (1H, m), 3.1-3.3 (1Ή, m), 3.7-3.8 (2H, m), 3.9-4.6 (13H, m) , 4.8-5.1 (8H, m), 5.11 (1H, d, J = 5.6Hz), 5.17 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz, 5.54 (1H, d, J = 5.9Hz), 6.7-6.9 (3H, m), 7.0-7.2 (3H, m) ), 7.3-7.5 (3H, m), 7.7-7.9 (8H, m), 8.02 (2H, d, J = 8.4Hz), 8.08 (1H, d) , J = 8.4Hz), 8.32 F. '. (1H, d, J = 7.7Hz), 8.81 (1H, d, J = 7.0Hz), 8.85 (1H, s). FAB MASS: m / z = 1309.3 (M +). Na)

Elemental Analysis calculated for C58H71N8022NaS-6H2O: C 49.92, H 6.00, N 8.03 Found: C 49.92, H 5.97, N 8.03

Example 47; IR (KBr): 3350, 2933, 1668, 1629, 1517, 1249, 1045 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.7Hz), 0.96 (3H) , d, J = 6.7Hz, 1.08 '(3H, d, J = 5.8Hz), 1.7-2.7 (8H, m), 3.1-3.3 (1H , m), 3.6-4.5 (16H, t11: m), 4.7-5.2 (8H, m), 5.18 (1H, d, J = 3.1Hz), 5.27 (1H, d, J = 4.5Hz) ;; 5.56 (1H, d, J = 5.8Hz), 6.7-7.0 (3H, m), 7.0-7.2 (3H, m), 7.2-7.5 ( 3H, m), 8.0-8.4 (6H, m), 8.85 (1H, s), 8.96 (1H, d, J = 7.0Hz), 9.07M (1H, s) ) FAB MASS: m / z = 1276.6 (M + Na +)

Elemental Analysis calculated for C54H72Ng022NaS-5H2O C 48.25, H 6.15, N 9.38 Found: C 48.10, H 6.14, N 9.30

Example 48 153 IR (KBr): 3350, 2931, 1668, 1629, 1537, 1049 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.9Hz), 0.9- 1.5 (16H, m), 1.6-2.4 (8H, m), 2.5-2.7 (1H, m), 3.1-3.3 (1H, m), 3, 5- ~ 5.6 (25H, m), 6.6-7.4 (8H, m), 7.8-8.4 (6H, m), 8.7-9.0 (2H, m) , 9.00 (1H, d, J = 2.4Hz) FAB MASS: m / z = 1331.4 (M + Na +).

Elemental Analysis calculated for C56H73N10O2NaS-8H2O C 46.28, H 6.17, N 9.64 Found: C 46.50, H 6.27, N 9.65

Example 49 IR (KBr pellet): 3300, 2931, 1668, 1650, 1629, 1538, 1515, 1268, 10 4 9 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6 , 6Hz), 0.97 (3H, d, J = 6.7Hz), 1.10 (3H, d, J = 5.6Hz), 1.2-1.4 (6H, m), 1.5 -1.7 (2H, m), 1.7-2.1 (3H, m), 2.1-2.4 (3H, m), 2.6-2.7 (3H, m), 3 , 1-3.2 (1H, m), 3.7-3.9 (2H, m), 3.9-4.5 (12H, m), 4.8-5.1 (7H, m) , 5.11 (1H, d, J = 5.5Hz), 5.18 (1H, d, J = 3.1Hz), 5.27 (1H, d, J = 4.5Hz), 5.55 ( 1H, d, J = 5.8Hz), 6.7-7.0 (3H, m), 7.06 (1H, s), 7.3-7.5 (5H, m), 7.72 ( 2H, d, J = 8.2Hz), 7.9-8.2 (5H, m), 8.3-8.4 (4H, m), 8.9-9.0 (2H, m) FAB -MASS: m / z = 1260, 5 (MH-Na +). Elemental analysis calculated for C 18 H 18 N 4 O 4 SNa 2 O 4: C 50, 58, H 5, 98, N 8.70 Found: C 50 , 34, H 6.16, N 8.55

Example 50 IR (KBr): 3369, 2958, 2935, 1670, 1629, 1525, 1473, 1247, 1047 cm -1 NMR (DMSO-d 6, δ): 0.95 (3H, t, J = 7.3Hz) , 0.97 (3H, d, J = 6.7Hz), 1.09 (3H, d, J = 5.7Hz), 1.3-1.6 (2H, m), 1.7-2, 1 (5H, m), 2.1-2.4 (3H, m), δ 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.7 -4.6 (15H, m), 4.7-5.1 (8H, m), 5.10 (1H, d, J = 5.6Hz), 5.18 (1H, d, J = 3, 1Hz), 5.26 (1H, d, J = 4.4Hz), 5.56 (1H, d, J = 5.7Hz), 6.7-7.0 (3H, m), 7.1- 7.2 (3H, m), 7.2-7.4 (3H, m), 7.70 (2H, d, J = 8.6Hz), 7.78 (2H, d, J = 8.4Hz) ), 8.1-8.4 (6H, m), 8.85 (1H, s), 8.99 (1H, d, J = 7.0Hz), 9.13 (1H, d, J = 1) , 6Hz) FAB MASS: m / z = 1310.1 (M + Na) +

Elemental Analysis calculated for C57H70N9022NaS-7H2O C 47.20, H 6.12, N 8.69 Found: C 47.42, H 6.19, N 8.92

Example 51 154 IR (KBr): 3351, 2937, 2875, 1670, 1627, 1533, 1245, 1047 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5.7Hz), 1.5-1.7 (2H, m), 1.7-2.1 (7H, m), 2.1-2.4 (3H) , m), 2.5-2.6 (1H, m), 3.1- 3.2 (1H, m), 3.7-3.8 (2H, m), 3.9-4.6 (15H, m), 4.7-4.9 (3H, m), 5.0-5.1 (5H, m), 5.10 (1H, d, J = 5.6Hz), 5.17 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.52 (1H, d, J = 5.9Hz), 6.7-7.1 ( 9H, m), 7.2-7.5 (5H, m), 7.68 (2H, d, J = 8.2Hz), 7.72 (2H, d, J = 6.7Hz), 7, 96 (2H, d, J = 8.2Hz), 8.06 (1H, d, J = 8.4Hz), 8.28 (1H, d, J = 7.7Hz), 8.76 (1H, d , J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1339.5 (M + Na +)

Elemental Analysis calculated for C 9 H 73 N 8 O 23 NaS-7H 2 O C 49.09, H 6.08, N 7.76 Found: C 49.04, H 6.08, N 7.82.

Example 52 IR (KBr): 3350, 2954, 2937, 1670, 1631, 1440, 1257, 1047 cm -1 NMR (DMSO-d 6, δ): 0.89 (3H, t, J = 6.8Hz), δ , 97 (3H, d, J = 6.7Hz), 1.09 (2H, d, J = 5.8Hz), 1.2-1.5 (6H, m), 1.7-2.1 ( 5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.2 (1H, m), 3.7-4, Δ (15H, m), 4.7-5.3 (1H, m), 5.5-5.6 (1H, m), 6.7-6.9 (1H, m), 7.0-. 7.5 (6H, m), 8.0-8.4 (8H, "m), 8.85 (1H, s), 8.96 (1H, d, J = 7.0Hz): T; APCI MASS: m / z = 1329.0 (M + Na) + [nu] Elemental analysis calculated for C56H71N10O23NaS -6H2O C 47.52, H 5.91, N 9.90 Found: C 47.42, H, 6.05; N, 9.90

Example 53 IR (KBr): 3350, 2952, 1666, 1629, 1537, 1519, 1255 cm -1 NMR (DMSO-d 6, δ): 0.89 (3H, t, J = 6.7Hz), δ, 96 (3H, d, J = 6.4Hz), 1.08 (3H, d, J = 5.6Hz), 1.7-2.4 (8H, m), 2.5-2.6 (1H , m), 3.7-4.5 (15H, m), 4.7-5.1 (8H, m), 5.11 (1H, d, J = 5.5Hz), 5.17 (1H , d, J = 3.1Hz, 5.26 (1H, d, J = 3.1Hz), 5.56 (1H, d, J = 5.7Hz), 6.73 (1H, d, J = 8.2Hz), 1:11: 6.7-7.0 (2H, m), 7.05 (1H, s), 7.13 (2H, d, J = 8.7Hz), 7.2- 7.5 (3H, m), 7.97 (2H, d, J = 8.7Hz), 8.1-8.4 (6H, m), 8.85 (1H, s), 8.92 ( 1H, 1d, J = 7.0Hz) m / z FAB MASS: m / z = 1345.3 (M + Na) +

Elemental Analysis calculated for C56H7N10O22S2Na-8H2O C 45, 84, H 5, 98, N 9.55.

Example 54 155 Found: C 45.87, H 6.07, N 9.55 IR (KBr pellet): 3350, 2931, 1670, 1652, 1628, 1442, 1247, 1047 cm -1 NMR (DMSO-d 6, δ ): 0.86 (3H, t, J = 6.6Hz), 0.97 (3H, d, J = 6.8Hz), 1.12 (3H, d, J = 6.8Hz), 1.2 -1.5 (10H, m), 1.7-2.0 (5H, m), 2.2-2.4 (3H, m), 2.5-2.6 (1H, m), 3 , 1-3.2 (1H, m), 3.72 (2H, lev), 3.8-4.5 (17H, m), 4.7-5.2 (9H, m), 5.26 (1H, d, J = 4.6Hz), 5.57 (1H, d, J = 5.7Hz), 6.7-7.1 (7H, m), 7.3-7.5 (3H, m) , 7.66 (2H, d, J = 8.7Hz), 8.10 (1H, d, J = 7.6Hz), 8.17 (1H, d, J = 7.6Hz), 8.76 ( 1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1293 (M + Na +).

Elemental Analysis calculated for C Cs ^H sNNNO ^ ^NSO ^ ^ ^O requires C 46.41, H 6.42, N 10.02 Found: C 46.51, H 6.43, N 9.95.

Example 55 IR (KBr): 3345, 2937, 1650, 1511, 1249, 1047 cm -1 NMR (DMSO-d 6, δ): 0.91 (3H, t, J = 7.0Hz), 0.96 (3H) , t, J = 7.8Hz), 1.09 (3H, d, J = 6.8Hz), 1.3-1.5 (4H, m), 1.6-2.1 (5H, m) , 2.1-2.5 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.7-3.9 (2H, m), 3.9-4.6 (13H, m), 4.79 (2H, d, J = 5.9Hz), 4.8-4.9 (1H, m), 4.9-5, Δ (5H, m), 5.10 (1H, δ "d, J = 5.9Hz), 5.17 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.6Hz), 5.53 (1H, d, J = 5.9Hz), 6.7-7.0 (3H, m), 7.0-7.2 (3H, m), 7.19 (1H, s), 7.3-7.5 (3H, m), 7.7-8.1 (6H, m), 8.08 (1H, d, J = 10.0Hz), 8.26 (1H, d, J = 8.8Hz), 8.77 (1H, m), 8.85 (1H, s), 13.32 (1H, s) FAB MASS: m / z = 1314.0. (M + Na) +: Elemental analysis calculated for C 56 H 71 N 10 O 2 SNa-8H 2 O: C 46, 86, H 6.11, N 9.76 Found: C, 46.93, H, 5.87, N, 9.74. 56 IR (KBr): 3350, 2958, 2935, 2873, 1666, 1629, 1247, 1045 cm -1 dd NMR (DMSO-d 6, δ): 0.9-1.1 (6H, m), 1 08 (3H, d, J = 6.0Hz), 1.4-1.6 (2H, m), 1.6-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (15H, m), 4, 7-5.1 (8H, m), 5.10 (1H, d, J = 5.5Hz), 5.17 (in, d, J = 2.9Hz), 5.25 (1H, d, J) = 4.5Hz), 5.55 (1H, d, J = 5.7Hz), 6.7-6.9 (3H, m), 7.0-7.5 (8H, m), 7.68 (2H , d, J = 8.9Hz), 7.73 (2H, d, J = 8.3Hz), 8.01 (2H, d, J = 8.3Hz), 8.10 (1H, d, J = 8.4Hz), 8.26 (1H, 156d, J = 7.7Hz), 8.8-9.0 (2H, m) FAB MASS: m / z = 1299.5 (M + Na) +

Elemental Analysis calculated for C56H69NB023NaS-6H2O C 48.55, H 5.89, N 8.09 Found: C 48.52, H 5.94, N 8.07

Example 57 IR (KBr): 3355.5, 1662.3, 1629.6, 1267.0 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.8Hz), δ , 93 (3H, d, J = 8.4Hz), 0.97 (3H, d, J = 6.7Hz), 1.2-1.5 (4H, m), 1.5-1.95 ( 5H, m), 2.1-2.45 (4H, m), 2.5-2.7 (4H, m), 3.17 (1H, m), 3.55-4.45 (14H, m), 4.6-5.3 (13H, m), 5.56 (1H, d, J = 5.6Hz), 6.72 (1H, d, J = 8.1Hz), 6.75 ( 1H, s), 6.77 (1H, d, J = 8.1Hz), 7.04 (1H, s), 7.10 (1H, s), 7.2-7.45 (10H, m) , 7.53 (4H, d, J = 6.6Hz), 7.85 (1H, d, J = 7Hz), 7.92 (1H, d, J = 7Hz), 8.05 (1H, d, J = 7Hz), 8.22 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1408 (M + Na)

Example 58 IR (KBr): 3347.8, 1664.3, 1631.5, 1245.8 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.6Hz), δ , 96 (3H, d, J = 6.6Hz), 1.04 (3H, d, J = 5.7Hz), 1.15-2.6 (21H, m), 3.16 (1H, m) , 3.5-4.5 (16H, m), 4.6-5.4 (13H, m), 5.47 (1H, d, J = 5.7Hz), 6.73 (1H, d, J = 8.2Hz) 6.78-6.85 (4H, m), 7.05 (1H, s), 7.10 (1H, s), 7.18 (2H, d, J = 8.6Hz) ), 7.25-7.45 (6H, m), 7.72 (1H, d, J = 7Hz), 7.91 (1H, d, 11 J = 7Hz), 8.05 (1H, d) , J = 9.3Hz), 8.20 (1H, d, J = 7Hz), 8.85 (1H, s). FAB MASS: m / z = 1390 (M + Na).

Elemental Analysis calculated for C 90 + 6 · Ng · C · SNa-S 1 · 0; C, 49.41; H, 6.36; N, 8.64 Found: C, 49.77; H, 6.71; N, 8.71; Example 59 IR (KBr): 3353.6, 1670.1, 1627.6, 1247.7 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.5Hz) , 0.97 (3H, d, J = 6.8Hz), 1.01: (3H, d, J = 5.4Hz), 1.1-1.55 (12H, m), 1.55-1. , 95 (5H, m), 2.05-4.7 /, (4H, m), 3.16 (1H, m), 3.5-4.5 (16H, m), 4.6-. 5.3 (13H, m), 5.55 (1H, d, J = 5.6Hz), 6.7-6.9 (5H, m), 7.05 (1H, s), 7.1 ( 1H, s), 7.15 (1H, d, J = 8.5Hz), 7.25-7.5 (6H, m), 7.73 (1H, d, J = 8.4Hz), 7, 92 (1H, d, J = 7Hz), 8.08 (1H, d, J = 8.4Hz), 8.18 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS : m / z = 1390 (M + Na) / 1 ·> Example 60 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.6Hz), 0.96 (3H, d, J = 6.6Hz), 1.05,157 (3H, d, J = 5.6Hz), 1.1-1.5 (22H, m), 1.5-2.5 (9H, m), 2, 5-3.5 (4H, m), 3.5-4.45 (14H, m), 4.45-5.45 (12H, m), 6.72 (1H, d, J = 8.2Hz) ), 6.79 (1H, s), 6.81 (1H, d, J = 8.2Hz), 7.04 (1H, s), 7.05-7.5 (8H, m), 7, 9-8.3 (3H, m), 8.84 (1H, s) FAB MASS: m / z = 1325 (M + Na)

Elemental Analysis calculated for C58H89N8022SNa -6H2O C 49.35, H 7.14, N 7.94 Found: C 49.33, H 7.04, N 7.87.

Example 61 IR (KBr): 3400, 1668.1, 1629.6, 1270.9 cm -1 NMR (DMSO-d6, δ): 0.96 (3H, d, J = 6.8Hz), 1.06 (3H, d, J = 5.7Hz), 1.1-2.0 (33H, m), 2.1-2.5 (4H, m), 3.20 (3H, s), 3.28 (2H, t, J = 6.5Hz), 3.1-3.3 (1H, m), 3.6-4.45 (14H, m), 4.6-5.3 (13H, m) , 5.49 (1H, d, J = 6.1Hz), 6.70 (1H, s), 6.72 (1H, d, J = 8.2Hz), 6.80 (1H, d, J = 8.2Hz), 7.03 (1H, s), 7.0-7.1 (1H, m), 7.15 (1H, s), 7.2-7.45 (6H, m), δ , 0-8.3 (3H, m), 8.83 (1H, s) FAB MASS: m / z = 1426 (M + Na).

Elemental Analysis calculated for C C tH ^ NNgC ^ SNNα-St StO requires C 49.82, H 7.01, N 8.43 Found: C 49.86, H 7.31, N 8.40.

Example 62: "IR (KBr): 3355.5, 1668.1, 1629.6, 1274.7 cm" 1: NMR (DMSO-d6, δ): 0.85 (3H, t, J = 6.5Hz ), 0.96 (3H, d, J = 6.7Hz), 1.04

II (3H, d, J = 5.9Hz), 1.1-2.6 (34H, m), 3.2 (1H, m), 3.6-4.55 (14H, m), 14 , 7-5.3 (11H, m), 5.47 (1H, d, J = 5.9Hz), 6.72 (1H, d, J = 8.1Hz), 6.79 (1H, s) , 6.81 (1H, d, J = 8.1 Hz), 7.05 (1H, s), 7.11 (1H, s), 7.2-7.5; (2H, m), 8.0-8.15 (2H, m), 8.20 (1H, d, J = 8.0Hz), 8.84 (1H, s) FAB MASS: m / z = 1235 (M + Na)

Elemental Analysis calculated for C CHHsiNNgC ^SNa ^ · H ^O requires C 45.73, H 7.15, N 8.37: Found: C 45.55, H 7.24, N 8.23

Example 63 '77 IR (KBr): 3353.6, 1664.3, 1627.6 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.6Hz), 0.95 (3H, d, J = 6.7Hz), 1.04 •; 7 (3H, d, J = 5.7Hz), 1.2-2.7 (30H, m), 3.16 (1H, m) ), 3.6-4.5 (13H, m),: 7.7 '. 4.7-5.3 (11H, m), 5.51 (1H, d, J = 6.0Hz), 5.74 (1H, s), 6.72 (1H, d, J = 8, 2Hz), 6.75 (1H, s), 6.77 (1H, d, J = 8.2Hz), 7.05 (1H, s), 7.2-7.5 (3H, m), δ , 0-8.3 (3H, m), 8.85 (1H, s) 158 FAB MASS: m / z = 1204 (M + Na)

Elemental Analysis calculated for C 50 H 77 N 8 O 2 SiSNa-5H 2 O C 47.24, H 6.90, N 8.81 Found: C 46.98, H 7.12, N 8.72.

Example 64 Main product IR (KBr): 3400, 1675.8, 1631.5, 1511.9, 1234.2 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.6Hz) ), 1.05 (3H, d, J = 5.8Hz), 1.2-1.6 (10H, m), 1.6-2.1 (5H, m), 2.1-2.7 (4H, m), 3.05-3.2 (4H, m), 3.20 (3H, s), 3.29 (2H, t, J = 6.4Hz), 3.3-3.5 (5H, m), 3.6-4.5 (15H, m), 4.7-5.3 (11H, m), 5.50 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.1 (9H, m), 7.2-7.5 (3H, m), 7.81 (2H, d, J = 8, 6Hz), 8.08 (1H, d, J = 8.2Hz), 8.24 (1H, d, J = 7Hz), 8.44 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1403 (M + Na)

Elemental Analysis calculated for C61H85N10O23SNa, 9H2O C 47.47, H 6.73, N 9, 07 Found: C 47.43, H 7.06, N 9.03

By-product IR (KBr): 3350, 1668.1, 1631.5, 1511, 9, 1234.2 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.6Hz), 1, 07 (3H, d, J = 5.8Hz), 1.2-1.5 (6H, m), 1.55-2.1 (7H, m), 2.1-2.65 (4H, m) ), 3.0-3.6 (9H, m), 3.7-4.5 (15H, m), 4.7-5.6 (14H, m), 5.7-6.0 (HI , m), 6.72 (1H, d, J = 8.0Hz), 6.75-7.1 (9H, m), 7.25-7.5 (3H, m), 7.81 (2H, d, J = 8.3Hz), 11.08.08 (1H, d, J = 8.2Hz), 8.25 (1H, d, J = 7Hz), 8.45 (1H, d, J = 7Hz), J V. 8.85 (1H, s) FAB MASS: m / z = 1371 (M + Na)

Elemental Analysis calculated for C30H11N2O4S4SNaSiO2: C 48.25, H 6.55, N 9.38 Found: C 48.10, H 6.81, N 9.40

Example 65 /: IR (KBr): 3450, 1668.1, 1635.3 cm -1, NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.5Hz), 0.96 (3H, d, J = 6.7Hz), 1.06 δ (3H, d, J = 6Hz), 1.2-1.5 (6H, m), 1.6-2.1 (5H, m) ), 2.1-2.7 (4H, m),

Hi 3.1-3.4 (9H, m), 3.6-4.5 (15H, m), 4.7-5.3 (11H, m), 5.49 (1H, d, J) = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H, m), 6.83 (2H, d, -: J = 9.0Hz) , 6.94 (2H, d, J = 9.0Hz), 7.04 (1H, s), 7.12 (1H, t, [delta]; J = 8.4Hz), 7.2-7.5 (3H, m), 7.65-7.8 (2H, m), 8.09 (1H, d, J = 8.4Hz), 8.25 (1H, d, J = 7Hz), 8.63 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1363 (M + Na)

Elemental Analysis calculated for C CsstbaFF ^N CO ^SNa · S ^O OO requires C, 48.67; H, 6.20; N, 9.79 Found: C, 48.83; H, 6.15; N, 9.74.159.

Example 66 IR (KBr): 3400, 1668.1, 1635.3, 1510.0, 1240.0 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.6Hz) , 1.2-1.5 (6H, m), 1.5-2.05 (5H, m), 2.1-2.65 (4H, m), 3.1-3.3 (9H, m), 3.6-4.5 (15H, m), 4.7- 5.3 (11H, m), 5.51 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz, 6.8-6.9 (4H, m), 6.94 (2H, d, J = 9.2Hz), 7.04 (1H, s), 7.24 ( 1H, d, J = 8.5Hz), 7.15-7.5 (3H, m), 7.86 (1H, dd, J = 8.6 and 2.1Hz), 8.02 (1H, d) , J = 2.1Hz), 8.04 (1H, d, J = 7.4Hz), 8.23 (1H, d, J = 7Hz), 8.70 (1H, d, J = 7Hz), δ , 84 (1H, s) FAB MASS: m / z = 1379 (M + Na)

Elemental Analysis calculated for C58H78ClN10O22SNa-6H2O C 47.52, H 6.19, N 9, 55 Found: C 47.78, H 6.23, N 9.55.

Example 67 IR (KBr): 3400, 1670 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.05 (3H, d, J = 5.7Hz) ), 1.4-2.65 (17H, m), 2.65-3.6 (8H, m), 3.6-4.5 (15H, m), 4.6-5.3 (11H) , m), 5.44 (1H, d, J = 6.0Hz), 6.73 (1H, d, J = 8.2Hz), 6.81 (1H, s), 6.83; , d, J = 8.2Hz), 6.98 (2H, d, J = 8.9Hz), 7.05 (1H, s), 7.2-7.5 (3H, m), 7, 80 (2H, d, J = 8.9Hz), 8.05 (1H, d, J = 8.4Hz), 8.26 (1H, d, J = 7Hz), 8.39 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1229 (M + Na)

Elemental Analysis calculated for C52H74N10O2iS-5H2O C 48.14, H 6.53, N 10.80 Found: C 48.29, H 6.33, N 10.95 <- Example 68/9 IR (KBr): 3400, 1652.7, 1635.3, 1511.9, 1241.9 cm -1, 1 H NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.6Hz), 0.97 (3H, d, J = 6.7Hz), 1.09-1 (3H, d, J = 5.7Hz), 1.2-1.5 (6H, m), 1.6-2.0 (5H, m), 2.1-2.6 (4H, m), 3.0-3.3 (5H, m), 3.6-4.6 (19H, m), 4.7-5 , 3 (1H, m), 5.53 (1H, d, J = 5.6Hz), 6.73 (1H, d, J = 8.2Hz), 6.75-7.0 (2H, m) ), 6.83 (2H, d, J = 9.2Hz), 6.95 (2H, d, J = 9.2Hz), 7.05 (1H, s), 7.12 (1H, s), 7.25-: Λ; 7.5 (2H, m), 7.42 (1H, d, J = 9.5Hz), 7.84 (1H, d, J = 9.5Hz), 7.9-. 8.1 (2H, m), 8.71 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1347 (M + Na)

Elemental Analysis calculated for C Csgt ^ ^ N ^ ^ ^ ^ ^ SNaa ^ F ^ ^ O C 46.34, H 6.32, N 11.58 Found: C 46.38, H 6.18, N 11.36.160.

Example 69 NMR (DMSO-d6, δ): 0.88 (3H, t, J = 6.6Hz), 0.97 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5.8Hz), 1.2-1.5 (6H, m), 1.6-2.05 (5H, m), 2.1-2.6 (4H, m), 3.0-3 , 3 (5H, m), 3.4-3.55 (4H, m), 3.7-4.6 (15H, m), 4.7-5.3 (UH, m), 5.52 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.1Hz), 6.8-6.95 (2H, m), 6.83 (2H, d, J = 9.3Hz), 6.95 (2H, d, J = 9.3Hz) 7.05 (1H, s), 7.14 (1H, s), 7.3-7.6 (3H, m), 7.84 (1H, d, J = 8.6Hz), 7.95-8.1 (2H, m), 8.40 (1H, s), 8.42 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1346 (M + Na)

Elemental Analysis calculated for C57H78N11O22SNa-5H2O C 48.40, H 6.27, N 10.89 Found: C 48.32, H 6.44, N 10.86

Example 70 IR (KBr): 3400, 1668.1, 1629.6, 1511.9 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.06 (3H, d, J = 5.7Hz), 1.15-1.5 (6H, m), 1.6-2.0 (7H, m), 2.1-2.65 (5H, m) , 3.1-3.5 (9H, m), 3.6-4.5 (13H, m), 4.7-5.3 (uH, m), 5.46 (1H, d, J = 5, 9Hz), 6.73 (1H, d, J = 8.2Hz), 6.81 (1H, s), 6.84 (1H, d, J = 8.2Hz), 6.91 (2H, d, : "J = 8.7Hz), 6.95-7.05 (3H, m), 7.09 (2H, d, J = 8.7Hz), 7.25-7.5 (3H, : m), 7.81 (2H, d, J = 8.8Hz), 8.09 (1H, d, J = 7Hz), 8.25 (1H, d, J = 7Hz), mm; 8.04 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1327 (M + Na)

Elemental Analysis calcd for C ^ NH NjoOjoClkiSNa-S ^ ^O: 1 C 49.92, H 6.28, N 10.03 Found: C 49.75, H 6.41, N 10.25.

Example 71: '1 IR (KBr): 3350, 1668.1, 1629, 6, 1511.9, 1232.3 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6 , 5Hz), 0.96 (3H, d, J = 6.7Hz), 1.06 '(3H, d, J = 6.0Hz), 1.2-1.4 (6H, m), 1.4-1.6 (2H, m), 1.7-2.1 (3H, m), k: 2.1-2.7 (6H, m), 3.1-3.5 (9H) , m), 3.72 (2H, m), 3.8-4.5 (UH, m), 4.7- 5.3 (UH, m), 5.47 (1H, d, J = 5.9Hz) ), 6.73 (1H, d, J = 8.2Hz), 6.8- 6.9 (2H, m), 6.91 (2H, d, J = 8.6Hz), 6.95 -7.15 (5H, m), 7.25-7.5 (3H,:, k; m), 7.81 (2H, d, J = 8.8Hz), 8.09 (1H, d, J = 8.4Hz), 8.26 (1H, d, J = 7Hz), 8.40 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1329 (M + Na)

Elemental Analysis calculated for C58H19N10NaO2iS-6H2O C 49.22, H 6.48, N 9.90 Found: C 49.33, H 6.67, N 9.89.161.

Example 72 IR (KBr): 3450, 1668.1, 1631.5, 1240.0 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.6Hz), 1.05 (3H, d, J = 5.6Hz), 1.7, 1.7 (414, m), 1.7-2.1 (7H, m), 2.1-2.73 (6H, m), 2 , 75-3.05 (4H, m), 3.05-4.5 (18H, m), 4.7-5.5 (12H, m), 6.72 (1H, d, J = 8, 3Hz), 6.77-6.9 (2H, m), 6.96 (2H, d, J = 8.6Hz), 7.05 (1H, s), 7.1-7.5 (8H, m), 7.80 (2H, d, J = 8.6Hz), 8.06 (1H, d, J = 8.4Hz), 8.28 (1H, d, J = 7Hz), 8.41 ( 1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1305 (M + Na)

Elemental Analysis calculated for C58H78N10O2S8, 8H2O requires C, 48.80; H, 6.64; N, 9.81 Found: C, 48.88; H, 6.50; N, 9.81.

Example 73 IR (KBr): 1673.9, 1646.9, 1510.0 1238.1 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.4Hz), δ, 96 (3H, d, J = 6.6Hz), 1.05 (3H, d, J = 5.6Hz), 1.2-1.5 (6H, m), 1.5-2.0 (9H) , m), 2.1-2.8 (uH, "m), 3.1-3.4 (5H, m), 3.4-4.5 (17H, m), 4.6-5 , Δ (12H, m), 6.6-7.0: (9H, m), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.78 (2H, d, J = 8.7Hz), 8.05 (1H, d, J = 8.4Hz), 8.24 (1H, d, J = 7Hz), 8.39 (1H, d, J = 7Hz), 8.84 (1H, s) FAB MASS: m / z = 1326 (M + -SO 3 + Na) 11 Elemental analysis calculated for C 63 H89 NNO 22 S 9 H 2 O: C 48, 92, H 6, 97, N 9, 96 Found: C, 48.77; H, 6.73; N, 9.94

EXAMPLE 74 IR (KBr): 3450, 1670.1, 1631.5, 1280.5 cm -1 1 H NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 7.0Hz), 0.96 (3H, t, J = 6.8Hz), 1.05 (3H, d, J = 5.6Hz), 1.1-1.65 (13H, m), 1.65-2.1 (7H, m), 2.1-2.65 (5H, m), 3.17 (1H, m), 3.6-4.5 (13H, m), 4.7-5.3 (11H) , m), 5.49 (1H, d, J = 5.9Hz), 6.72 (1H, d, J = 8.2Hz), 6.82 (1H, d, J = 8.2Hz), 6 , 84 (1H, 'Vt s), 7.04 (1H, s), 7.29 (2H, d, J = 8.3Hz), 7.2-7.5 (3H, m), 7.80 (2H, d, J = 8.3Hz), 8.10 (1H, d, J = 8.4Hz), 8.26 (1H, d, J = 7Hz), 8.65 (1H, d, J = 7Hz), 8.84 (1H, s) 162 FAB MASS: m / z = 1237 (M + Na)

Elemental Analysis calculated for C53H75N802iSNa-6H2O C 48.10, H 6.63, N 8.47 Found: C 48.26, H 6.62, N 8.46.

Example 75 IR (KBr): 3400, 1670.1, 1627.6, 1272.8 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 3.3Hz), 1.08 (3H, d, J = 5.7Hz), 1.2-1.6 (10H, m), 1.6-2.1 (5H, m), 2.1-2.7 (4H, m) , 3.0-3.3 (1H, m), 3.20 (3H, s), 3.29 (2H, t, J = 6.4Hz), 3.73 (2H, m), 3.9 -4.6 (13H, m), 4.7-5.3 (11H, m), 5.53 (11-1, d, J = 5.8Hz), 6.73 (1H, d, J = 8.3Hz), 6.83 (1H, d, J = 8.3Hz), 6.91 (1H, s), 7.05 (1H, s), 7.23 (1H, dd, J = 9, 0 and 2.3Hz), 7.3-7.5 (4H, m), 7.8-8.0 (3H, m), 8.09 (1H, d, J = 8.4Hz), 8, 33 (1H, d, J = 7Hz), 8.44 (1H, s), 8.80 (1H, d, J = 7Hz), 8.85 (1H, s) FAB MASS: m / z = 1293 (M + Na)

Elemental Analysis calculated for C55H75N8023SNa-6H2O C 47.89, H 6.36, N 8.12 Found: C 47.81, H 6.26, N 8.05

Example 76 IR (KBr): 3361.3, 1668.1, 1635.3, 1627.6 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6.7Hz), δ , 96 (3H, d, J = 6.7Hz), 1.09 (3H, d, J = 5.8Hz), 1.19-1.25 (8H, m), 1.25-2.00 ( 5H, m), 2.02-2.53 '(4H, m), 2.44 (3H, s), 2.61 (2H, t, J = 7.6Hz), 3.05-3, 27 (1H, m), δ 1.55-4.50 (13H, m), 4.65-5.65 (12H, m), 6.42 (1H, s), 6.65-. 6.95 (3H,; 11 '; m), 7.05 (1H, d, J = 0.4Hz), 7.13-7.50 (5H, m), 7.50-7.88 (6H). , m), 1; 8.10 (1H, d, J = 9.0Hz), 8.25 (1H, d, J = 8.4Hz), 8.40 (1H, d, J = 7.0Hz), 8.85 (1H , s) FAB MASS: m / z = 1299.3 (M + Na-1): Elemental analysis calculated for C58H77N8NaO21S-5H2O C 50.94, H 6.41, N 8.19 Found: C 50 , 99, H, 6.40, N, 8.15, 11: Example 77 IR (Nujol): 3351.7, 1670.1, 1652.7, 1623.8 cm -1: 1 H NMR (DMSO-d 6, δ ): 0.86 (3H, t, J = 6.7Hz), 0.96 (3H, d, J = 6.7Hz), 1.06 / (3H, d, J = 5.8Hz), 1, 13-1.45 (8H, m), 1.47-1.96 (5H, m), 2.06-2.66 (8H, m), 2.81 (2H, t, J = 7.6Hz) ), 3.04-3.30 (1H, m), 3.53-4.50 (13H,:; m), 4.53-5.70 (12H, m), 6.64-6, 88 (3H, m), 7.04 (1H, d, J = 0.4Hz), 7.13-7.60 (11H, m), 8.10 (1H, d, J = 9.0Hz), 8.18 (1H, d, J = 8.4Hz), 8.30 (1H, d, J = 7.0Hz), 8.85 (1H, s) 163 FAB MASS: m / z = 1287.4 (M + Na-1)

Elemental Analysis calculated for C57H77N8NaO2iS, 5H2O C 50.51, H 6.46, N 8.27 Found: C 50.84, H 6.60, N 8.33.

Example 78 IR (KBr): 3361.3, 1683.6, 1670.1, 1662.3, 1652.7, 1646.9, 1635.3, 1627.6, 1623.8 cm -1 NMR (DMSO-d , δ): 0.97 (3H, d, J = 6.7Hz), 1.07 (3H, d, J = 5.6Hz), 1.28-2.00 (13H, m), 2.08 -2.60 (4H, m), 3.07-3.30 (1H, m), 3.60-4.66 (17H, m), 4.66-5.12 (9H, m), δ , 11 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.6Hz), 5.52 (1H, d, J = 6.0Hz), 6, 62-6, 95 (4H, m), 6.95-7.15 (3H, m), 7.20-7.50 (3H, m), 7.50-7.85 (7H, m), 8.12 ( 1H, d, J = 8.4Hz), 8.35 (1H, d, J = 7.7Hz), 8.53 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1319.7 (M + Na-1).

Elemental Analysis calculated for C57H74N8NaC? 22SF-8H2O C 47.49, H 6.29, N 7.77 Found: C 47.79, H 6.16, N 7.93

Example 79 IR (KBr): 3354.9, 1668.1, 1662.3, 1654.6, 1646.9, 1627.6 cm-1 NMR (DMSO-d6, δ): 0.85 (3H, t, J = 6.7Hz), 0.90-1.10 (6H, m), 1.10-1.40: (8H, m), 1.48-1.95 (5H, m), 2.05- 2.46 (4H, m), 2.60 (2H, t, V: J = 7.6Hz), 3.07-3.23 (1H, m), 3.55-4.45 (14H, m) ), 4.67-5.32 (11H, m), 5.48-5.63 (1H, m), 6.22 (1H, J = 5.3Hz), 6.65-6.89 ( 3H, m), 6.97-7.15 (2H, m), 7.20-7.68 (10H, m), 7.85-8.20 (3H, m), 8.84 (1H, s) FAB MASS: m / z = 1289.4 (M + Na-1) • "Elemental Analysis calculated for C56H75N8NaO22S-3H2O / C 50.90, H6.18, N8, 48 Found: C50H22. 80, H 6.44, N 8.29

Example 80 IR (KBr): 3361.3, 1664.3, 1631.5, 1600.6 cm -1 -1 H NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6, 7Hz), 0.98 (3H, d, J = 6.7Hz), 1.16 (3H, t, J = 5.9Hz), 1.20-1.45 (8H, m), 1.50- 1.70 (2H, m), 1.70-2.05 (3H, m), 2.10-2.57 (4H, m), 2.63 (2H, t, J = 7.6Hz) ), 3.10-3.30 (1H, 1 'm), 3.68-4.50 (13H, m), 4.78-5.32 (11H, m), 5.66 (1H , d, J = 5.7Hz), δ, 6.68-7.02 (3H, m), 7.04 (1H, d, J = 0.4Hz), 7.25-7.48 ( 4H, m), 7.60-8.08 (7H, m), 8.10 (1H, d, J = 7.4Hz), 8.28 (1H, d, J = 7.7Hz), 8, 85 (1H, s), 9.30 (1H, d, J = 7.1Hz) 164 FAB MASS: m / z = 1287.5 (M + Na-1).

Elemental Analysis calculated for C55H73N8NaO22S-3H2O C 50.53, H 6.09, N 8.57 Found: C 50.66, H 6.01, N 8.22.

Example 81 IR (KBr): 3349.7, 1668.1, 1627.6 cm -1 NMR (DMSO-d6, δ): 0.85 (3H, t, J = 6.7Hz), 0.96 (3H, d , J = 6.7Hz), 1.09 (3H, d, J = 5.8Hz), 1.18-1.48 (8H, m), 1.50-2.10 (5H, m), 2 , 10-2.45 (3H, m), 2.50-2.65 (1H, m), 2.77 (2H, t, J = 7.6Hz), 3.05-3.25 (1H, m), 3.60-4.65 (13H, m), 4.67-5.60 (12H, m), 6.65-6.97 (3H, m), 7.05 (1H, d, J = 0.4Hz), 7.21-7.43 (4H, m), 7.76 (1H, s), 7.83-8.05 (3H, m), 8.10 (1H, d, J = 9.0Hz), 8.29 (1H, d, J = 8.4Hz), 8.48 (1H, s), 8.64-9.03 (2H, m) FAB MASS: m / z = 1233.0 (M + Na-1)

Elemental Analysis calculated for C 53 H 71 N 8 Na 2 O 5 S-3H 2 O C 50.96, H 6.22, N 8.96 Found: C 50.62, H 6.40, N 8.92

Example 82 IR (KBr): 3361.3, 1670.1, 1627.6 cm -1 NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 6.7Hz), 0.96 (3H) , d, J = 6.7Hz), 1.09 (3H, d, J = 5.9Hz), 1.18-1.43 (6H, m),. 1.50-2.10 (5H, m), 2.10-2.69: (4H, m), 2.77 (2H, t, J = 7.6Hz), 3.07-3.29 ( 1H, m), 3.60-4.62 (13H, V: m), 4.69-5.23 (10H, m), 5.27 (1H, d, J = 4.5Hz), δ, 55 (1H, d, J = 5.9Hz), 6.68-7.00 (3H, m), 7.05 (1H, d, J = 0.4Hz), 7.25-7.53 (4H , ,,, j; m), 7.76 (1H, s), 7.84-8.05 (3H, m), 8.13 (1H, d, J = 8.4Hz), 8.33 ( 1H, d, J = 7.7Hz), 8.48 (1H, s), 8.73-9.00 (2H, m) I FAB MASS: m / z = 1219.4 (M + Na-1). ) <l! Elemental Analysis calculated for C52H69N8NaO2iS-5H2O C 48.51, H 6.19, N 8.71. Found: C 48.67, H 6.34, N 8.74 •, Example 83 '' IR KBr): 3357.5, 1668.1, 1627.6 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 6.7Hz), 1.07 (3H, d, J = 6.0Hz), 1.20-1.62 (10H, m), 1.62-2.00 (5H, m), 2.10-2.65 (4H, m), 3.20 (3H) , s), δ 3.08-3.45 (1H, m), 3.28 (2H, t, J = 6.5Hz), 3.53-4.50 (15H, m), 4.68 - 1.1.13 (9H, m), 5.17 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.4Hz), 5.53 (1H, d, J = 6.0Hz, 6.68-6.95 (4H, m), 6.95-7.11 (3H, m), 7.20-7.52 (3H, m), 7, 55-7.95 (7H, m), 8.13 (1H, d, J = 8.4Hz), 8.30 (1H, d, 165 J = 7.7Hz), 8.52 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1345.2 (M + Na-1)

Elemental Analysis calculated for C38H19NgNaOgsS'SHgO C 48.29, H 6.53, N 7, 64 Found: C 48.44, H 6.58, N 7.75.

Example 84 IR (KBr): 3353.6, 1662.3, 1627.6 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.07 (3H) , d, J = 5.5Hz), 1.40-1.65 (2H, m), 1.65-2.00 (5H, m), 2.00-2.67 (6H, m), 3 , 08-3.30 (1H, m), 3.50-4.50 (15H, m), 4.68-5.13 (11H, m), 5.18 (1H, d, J = 3, 1Hz), 5.26 (1H, d, J = 4.5Hz), 5.53 (1H, d, J = 6.0Hz), 5.70-6.00 (1H, m), 6, 63- 6.95 (4H, m), 6.95-7.13 (3H, m), 7.20-7.52 (3H, m), 7.52-7.95 (7H, m), δ, 12 (1H, d, J = 8.4Hz), 8.31 (1H, d, J = 7.7Hz), 8.53 (1H, d, J = 7.0Hz), 8.85 (1H, s) ) FAB MASS: m / z = 1285.4 (M + Na-1)

Elemental Analysis calculated for C18H11NgO2SNa-SH2O C 47.79, H 6.23, N 7.96 Found: C 47.59, H 6.32, N 8.06

Example 85 IR (KBr): 3363.2, 1670.1, 1627.6 cm -1 NMR (DMSO-d 6, δ): 0.89 (6H, d, J = 6.5Hz), 0.96 (3H) , d, J = 6.7Hz, 1.07: '(3H, d, J = 5.7Hz), 1.22-1.41 (2H, m), 1.50-1.97 (6H, m), 2.11-2.65 v: (4H, m), 3.10-3.30 (1H, m), 3.60-4.50 (15H, m), 4.70-5, 08 (8 H, m); ''; 5.10 (1H, d, J = 5.6Hz), 5.16 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.5Hz), 5.50 ( 1H, d, J = 5.9Hz), 6.65-6.92 (4H, m), 6.92-7.12 (3H, m), 7.21-7.50 (3H, m). ), 7.52-7.90 (7H, m), 8.12 (1H, d, J = 8.4Hz), 8.30 (1H, d,; J = 7.7Hz), 8.56 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1287.6 (M + Na-1).

Elemental Analysis calculated for C56H73N8Na022S-6.5H2O, C 48.66, H 6.27, N 8.11: Found: C 48.67, H 6.32, N 8.20, Example 86 IR (KBr) ): 3361.3, 1683.6, 1670.1, 1654.6, 1635.3, δ 162 3.8 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 6) , 7Hz), 1.07 (3H, d, J = 5.6Hz), 1.30-V, 2.00 (11H, m), 2.10-2.70 (4H, m), 3, 05-3.15 (1H, m), 3.55-4.70 (17H, m), 4.70-5.11 (9H, m), 5.16 (1H, d, J = 3, 1Hz), 5.25 (1H, d, J = 4.5Hz), 5.52 (1H, d, J = 6.0Hz), 6.65-6.95 (4H, m), 6.95-. 7.10 (3H, m), 7.10 - 166 7.50 (3H, m), 7.50 - 7.85 (7H, m), 8.12 (1H, d, J = 8.4Hz) , 8.30 (1H, d, J = 8.3Hz), 8.52 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1305.2 (M + Na-1)

Elemental Analysis calculated for C56H12N8NaO22SF-6H2O C 48.34, H 6.09, N 8.05 Found: C 48.47, H 6.29, N 7.95.

Example 87 IR (KBr): 3359.4, 1668.1, 1654, δ, 1625.7 cm -1 NMR (DMSO-d6, δ): 0.97 (3H, d, J = 6.7Hz), , 07 (3H, d, J = 6.0Hz), 1.22-1.62 (6H, m), 1.62-2.00 (5H, m), 2.10-2.65 (4H, m), 3.20 (3H, s), 3.05-3.40 (1H, m), 3.31 (2H, t, J = 6.5Hz), 3/60-4.55 (15H, m), 4.65-5.13 (9H, m), 5.16 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.4Hz), 5.53 ( 1H, d, J = 6.0Hz), 6.68-6.95 (4H, m), 6.95-7.20 (3H, m), 7.20-7.58 (3H, m), 7.58-7.90 (7H, m), 8.13 (1H, d, J = 8.4Hz), 8.32 (1H, d, J = 7.7Hz), 8.53 (1H, d) , J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1317.6 (M + Na-1)

Elemental Analysis calculated for C57H75N8NaO23S-7H2O C 48.16, H 6.31, N 7.88 Found: C 48.21, H 6.60, N 7.78.

Example 88 IR (KBr): 3350, 2954, 1668, 1629, 1538, 1511, 1454, 1249 cm -1: 1 H NMR (DMSO-d 6, δ): 0.88 (3H, t, J = 7.1 Hz) ), 0.96 (3H, d, J = 7.5Hz), 1.08: (2H, d, J = 5.7Hz), 1.2-1.5 (6H, m), 1.6 -2.4 (8H, m), 2.6-2.7 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (19H, m), 4.7-5.3 (8H, m), 6.73 (1H, d, J = 8.2Hz), 6.8-7.1 (5H, m), 7.19 (1H, s) , 7.3-7.5 (3H, m), 7.75 (2H, d, J = 8.7Hz), 7.8-8.0 (4H, m), 8.08 (1H, d, J = 8.9Hz), 8.30 (1H, d, J = 7.7Hz), 8.7-9.0 (3H, m) FAB MASS: m / z = 1327 (M + Na +).

Elemental Analysis calculated for C57H73N10O22NaS-9H2O, C 46.65, H 6.25, N 9.54-11 found: C 46.95, H 6.22, N 9.55, Example 89 IR (KBr) : 3376, 2931, 2858, 1662, 1631, 1521, 1444, 1245, 1047 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 6.7Hz), 1.09 (3H) , d, J = 5.9Hz), 1.3-1.6 (6H, m), 1.7-2.1 (5H, m), 2.2-2.4 (3H, m), 2 , 5-2.6 (1H, m), 3.21; (3H, s), 3.2-3.4 (3H, m), 3.6-4.5 (16H, m), 4.79 (2H, d, J = 6.0Hz), 4.9 -5.2 (5H, m), 5.10 (1H, d, J = 3.6Hz), 5.18 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.53 (1H, d, J = 6.0Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-167 7.0 (2H, m), 7 , 0-7.2 (3H, m), 7.3-7.5 (3H, m), 7.6-7.9 (8H, m), 8.01 (2H, d, J = 8, 4 H 2), 8.12 (1H, d, J = 7.4Hz), 8.31 (1H, d, J = 7.7Hz), 8.79 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1367 (M + Na +)

Elemental analysis calculated for C ^ tH ^ NNsC ^ NaNSO ^, 5H20O requires C, 50.10; H, 6.20; N, 7.66 Found: C, 50.09; H, 6.17; N, 7.62.

Example 90 IR (KBr): 3363, 2937, 2869, 1646, 1444, 1255 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 6.7Hz), 1.08 (3H) , d, J = 5.7Hz), 1.2-1.6 (10H, m), 1.7-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5 -2.7 (1H, m), 3.20 (3H, s), 3.2-3.4 (1H, m), 3.6-4.6 (16H, m), 4.7-5 , 2 (8H, m), 5.16 (1H, d, J = 3.1Hz), 5.24 (1H, d, J = 4.5Hz), 5.54 (1H, d, J = 5, 8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H, m), 7.1-7.4 (6H, m), 7.97 (2H, d, J = 8.8Hz), 8.0-8.4 (6H, m), 8.84 (1H, s), 8.92 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1403.6 (M + Na +)

Elemental Analysis calculated for C59H77N10O23NaS2.16H2O C 47.58, H 6.02, N 9.40 Found: C 47.72, H 6.12, N 9.42

Example 91; IR (KBr): 3350, 1668, 1654, 1625, 1537, 1521, 1245, "1047 cm -1: NMR (DMSO-d 6, δ): 0.9-1.1 (6H, m), 1 , 07 (3H, d, J = 5.7Hz), 1.4-2.0 (7H, m), 2.2-2.5 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (16H, m), 4.7-5.1 (7H, m), 5.09 (1H, d, J = 5.6Hz), 5.16 (1H, d, J = 3, 1Hz), 5.25 (1H, d, J = 4.4Hz), 5.53 (1H, d, J = 6 , 0Hz), 6.73 (1H, d, J = 8.4Hz), 6.8-7.2 (6H, m) 7.2-7.5 (4H, m), 7.5-7 , Δ (6H, m), 8.11 (1H, d, J = 7.4Hz), 8.32 (1H, d, J = 7.7Hz), 8.54 (1H, d, J = 7, 0Hz), 8.84 (1H, S) FAB MASS: m / z = 1259 (M + Na +)

Elemental Analysis calculated for C54H69N8022NaS-8H2O: C, 46.95; H, 6.20; N, 8.11 Found: C, 47.20; H, 6.23; N, 8.28. Example 92; IR (KBr): 3359, 2929, 2852, 1668, 1650, 1631, 1538, 1515 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1 , 09 (3H, d, J = 6, 1Hz), 1.2-1.6 (5H, m), 1.6-2.5 (10H, m), 2.5-2.6 (1H, m) , 3.18 (1H, m), 3.7- 168 4.5 (15H, m), 4.8-5.2 (8H, m), 5.17 (1H, d, J = 3, 1Hz), 5.26 (1H, d, J = 4.5Hz), 5.55 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.1Hz), 6, 81 (1H, s), 6.85 (1H, s), 7.05 (1H, s), 7.2-7.4 (3H, m), 7.45 (2H, d, J = 8, 2Hz), 7.96 (2H, d, J = 8.2Hz), 8.0-8.2 (4H, s), 8.2-8.3 (1H, m), 8.85 (1H, s), 8.9-9.0 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1327.5 (M + Na) +

Elemental Analysis calculated for Ο56Η69Νι0θ2ΐ32Ν3 · 6Η2θ C 47.59, H 5.78, N 9, 91 Found: C 47.89, H 5.76, N 9.93

Example 93 IR (KBr): 3350, 1654, 1629, 1517, 1249, 1047 cm -1 NMR (DMSO-d 6, δ): 0.9-1.1 (6H, m), 1.11 (3H, d) , J = 5.9Hz), 1.6-2.0 (5H, s), 2.1-2.4 (3H, s), 2.6-2.7 (1H, m), 3.1 -3.3 (1H, m), 3.6-4.5 (16H, m), 4.7-5.2 (7H, m), 5.10 (1H, d, J = 5.6Hz) , 5.17 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.5Hz), 5.55 (1H, d, J = 5.7Hz), 6.7- 6.9 (3H, m), 7.0-7.5 (6H, m), 7.74 (2H, d, J = 8.8Hz), 7.91 (2H, d, J = 8.5Hz) ), 8.1-8.4 (8H, m), 8.84 (1H, s), 8.97 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1363.5 ( M + Na) +

Elemental Analysis calculated for C59H69N10O23SNa, 5H2O requires C, 49.51; H, 5.56; N, 9.79 Found: C, 49.39; H, 5.63; N, 9.77.

Example 94 V: IR (KBr): 3355, 2929, 2856, 1664, 1631, 1519, 1440, 1282 cm -1 NMR (DMSO-d 6, δ): 0.84 (3H, t, J = 6.7Hz) , 0.96 (3H, d, J = 6.7Hz), 1.07 (3H, t, J = 5.8Hz), 1.2-1.5 (12H, m), 1.7-2, 0 (5H, m), 2.2-2.4 (3H, m), 2.5-2.7 (1H, m), 2.94 (2H, t, J = 7.4Hz), 3, 1-3.3 (1H, m), 3.6-4.6 (14H, m), 4.8-5.2 (7H, m), 5.10 (1H, d, J). = 3.6Hz), 5.17 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.55 (1H, d, J = 5.9Hz) ), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H, m), 7.0-7.5 (4H, m), 8.0-8, 2 (5H, m), 8.27 (1H, d, J = 7.7Hz), 8/85 (1H, s), 8.93 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1279 (M + Na +)

Elemental Analysis calculated for C53H73N10O22SNa -5.5H2O C 46.93, H 6.24, N 10.33 Found: C 46.93, H 6.46, N 10.31,; Example 95 1: IR (KBr): 3363, 1673, 1648, 1538, 1253 cm -1 NMR (DMSO-d 6, δ): 0.92 (3H, t, J = 6.8Hz), 0.97 (3H) , d, J = 6.8Hz), 1.10 (3H, d, J = 5.8Hz), 1.2-1.5 (6H, m), 1.7-2.1 (5H, m) , 2.1-2.4 (3H, m), 169 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (16H) , m), 4.7-5.1 (9H, m), 5.16 (1H, d, J = 3.1Hz), 5.24 (1H, d, J = 4.5Hz), 5.54 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.4 (8H, m), 8.04 (2H, d, J = 8.8Hz), 8.13 (2H, d, J = 8.6Hz), 8.2-8.4 (4H, m), 8.84 (1H, s), 8.98 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1329.6 (M + Na) +

Elemental Analysis calculated for C56H7N10O23SNa -7H2O C 46.92, H 5.97, N 9.77 Found: C 46.86, H 5.99, N 9.77.

Example 96 IR (KBr): 3355, 2929, 1666, 1648, 1631, 1515, 1442, 1047 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.7Hz), δ , 97 (3H, d, J = 6.7Hz), 1.10 (3H, d, J = 5.8Hz), 1.2-1.5 (10H, m), 1.7-2.1 ( 5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.6-4, Δ (16H, m), 4.79 (2H, d, J = 5.9Hz), 4.8-5.2 (5H, m), 5.09 (1H, d, J = 5.5Hz), 5.16 (1H, d, J = 3.1Hz), 5.23 (1H, d, J = 4.5Hz), 5.53 (1H, d, J = 5.9Hz), 6.73 (1H , d, J = 8.0Hz), 6.8-6.9 (2H, m), 7.0-7.5 (6H, m), 7.97 (2H, d, J = 8.8Hz) , 8.0-8.3 (6H, m), 8.83 (1H, s), 8.88 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1373.5 (M + Na)

Elemental Analysis calculated for C58H75N10O2S2Na-6H2O C 47.73, H 6.01, N 9.60.1 Found: C 47.57, H 5.92, N 9.53 <1.1 <Example 97 IR (KBr): 3361 , 2925, 2852, 1668, 1650, 1631, 1538, 1452, 1049 cm -1; NMR (DMSO-d6, δ): 0.87 (3H, t, J = 6.9Hz), 0.96 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5 , 7Hz), 1.2-1.4 (1H, m), 1.4-1.6 (2H, m), 1.7-2.1 (5H, m), 2.1-2.5 (5H, m), 2.5-2.6 (1H, m), 3.1-3.3 (2H, m), 3.7-4.5 (14H, m), 4.7-5 , Δ (7H, m), 5.09 (1H, d, J = 5.6Hz), 5.16 (1H, d, J = 3.1Hz), δ 5.25 (1H, d, J = 4.5Hz), 5.54 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H, d), 7, 04 (1H, s), 7.2-7.5 (3H, m), 8.03 (4H, s), 8.0- 8.3 (2H, m), 8.84 (1H, s) , 8.95 (1H, d, J = 7.0Hz), 7 FAB MASS: m / z = 1321.9 (M + Na) + 1 'Elemental analysis calcd. H, 6.17; N, 10.08; found: C, 47.38; H, 6.12; N, 9.98.

Example 98 170 IR (KBr): 3374, 2937, 2875, 1658, 1629, 1531, 1436, 1255, 1047 cm -1 NMR (DMSO-d 6, δ): 0.9-1.11 (6H, m), 1.09 (3H, d, J = 5.7Hz), 1.2-1.5 (4H, m), 1.7-2.1 (5H, m), 2.2-2.5 (3H) , m), 2.6-2.7 (1H, m), 3.2-3.3 (1H, m), 3.6-4.5 (16H, m), 4.80 (2H, d) , J = 5.8Hz), 4.8-5.2 (5H, m), 5.10 (1H, d, J = 5.5Hz), 5.17 (1H, d, J = 3.0Hz) , 5.24 (1H, d, J = 4.5Hz), 5.53 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8- 7.0 (2H, m), 7.06 (1H, s), 7.10 (2H, d, J = 8.9Hz), 7.2-7.5 (3H, m), 7.68 ( 1H, s), 7.86 (2H, d, J = 8.8Hz), 8.0-8.4 (6H, m), 8.84 (1H, s), 8.90 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1314 (M + Na +)

Elemental Analysis calculated for C56H90N9023NaS-6H2O C 48.03, H5, 90, N9.00 Found: C, 47.92; H, 5.83; N, 8.88.

Example 99 IR (KBr): 3345, 1646, 1633, 1531, 1257 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 6.7Hz), 1.11 (3H, d) , J = 5.7Hz), 1.2-1.6 (10H, m), 1.7-2.5 (8H, m), 2.6-2.7 (1H, m), 3.21 (3H, s), 3.3-3.4 (1H, m), 3.7-4.6 (16H, m), 4.8-5.2 (8H, m), 5.16 (1H , d, J = 3.1Hz), 5.24 (1H, d, J = 4.5Hz), 5.55 (1H, d, J = 5.7Hz), 6.7-6.9 (3H, m), 7.0-7.5 (6H, m), 8.0-8.3 (8H, m), 8.84 (1H, s), 8.96 (1H, d, J = 7, 0Hz): FAB MASS: m / z = 1387.7 (M + Na +). Elemental analysis calcd. C 48.09, H 6, 09, N 9, 51 [(i '; Found: C 47.81, H 5.83, N 9.38;) Example 100 IR (KBr): 3357, 1668, 1631; 1429, 1284, 1047 cm -1 NMR (DMSO-d6, δ): 0.97 (3H, d, J = 6.7Hz), 1.09 (3H, d, J = 5.8Hz), 1, 8-: 2.4 (6H, m), 2.5-2.6 (1H, m), 3.1-3.2 (1H, m), 3.7-4.6 (14H, m) , 4.7-5.2 (7H, m), 5.10 (1H, d, J = 5.5Hz), 5.17 (1H, d, J = 3.1Hz), 5.24 (1H, d, J = 5.5Hz), 5.53 (1H, d, J = 5.8Hz), 6.75 (1H, d, J = 8.2Hz), 6.8-6.9 (2H, m ), 7.05 (1H, s), 7.3-7.6 (9H, m), 7.8-7.9 (4H, m), 8.0-8.2 '1'. ( 5H, m), 8.2-8.3 (1H, m), 8.34 (1H, d, J = 9.3Hz), 8.7-8.8 (1H, m), 8.85 ( 1H, s) • .N FAB MASS: m / z = 1332.7 (M + Na +) ','; Elemental Analysis calculated for C58H65N10O22SNa-8H2O C 47.93, H5, 62, N9, 64 Found: C, 47.83; H, 5.53; N, 9.56

Example 101 171 IR (KBr): 3353, 2929, 2856, 1666, 1631, 1612, 1496, 1440, 1259 cm -1 1 H NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 6.6Hz) ), 0.97 (3H, d, J = 6.5Hz), 1.09 (3H, d, J = 5.9Hz), 1.2-1.5 (10H, m), 1.7-2 , 1 (5H, m), 2.2-2.5 (3H, m), 2.6-2.7 (1H, m), 3.1-3.2 (1H, m), 3.6 -4.5 (16H, m), 4.7-5.0 (3H, m), 5.0-5.2 (5H, m), 5.10 (1H, d, J = 3.1Hz) , 5.26 (1H, d, J = 4.2Hz), 5.56 (1H, d, J = 5.5Hz), 6.73 (1H, d, J = 8.1Hz), 6.8- 7.0 (2H, m), 7.05 (1H, s), 7.1-7.5 (5H, m), 8.0-84 (8H, m), 8.85 (1H, s) , 8.95 (1H, d, J = 7.0Hz) FAB-MASS: m / z = 1357.3 (M + Na +)

Elemental Analysis calculated for C CsgHvsNNCkaNaS ^ i ^ ^O requires C 47.67, H 6.14, N 9.58 Found: C 47.63, H 6.42, N 9.52.

Example 102 IR (KBr): 3361, 1670, 1648, 1633, 1540, 1519, 1249 cm -1 1 H NMR (DMSO-d 6, δ): 0.89 (3H, t, J = 7.0Hz), 0.97 (3H, d, J = 6.8Hz), 1.10 (3H, d, J = 5.7Hz), 1.2-1.5 (6H, m), 1.6-2.4 (8H, m), 2.5-2.7 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (16H, m), 4.80 (2H, d, J = 5.8Hz), 4.8-5.2 (5H, m), 5.10 (1H, d, J = 5.4Hz), 5.18 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.3Hz), 5.55 (1H, d, J = 5.7Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7 , 0 (2H, m), 7.0-7.5 (6H, m), 8.02 (1H, d, J = 5.3Hz), 8.0-8.4 (4H, m), δ , 42 (2H, d, J = 8.4Hz), 8.48 (2H, d, J = 8.9Hz), 8.8-9.0 (3H, m) '' FAB MASS: m / z = 1339.3 (M + Na +). Analysis for Elemental Calcd for C 6 H 12 N 4 O 4 N 4 O 6 N 8 O 4 C 48.87, H 6.01, N 9, 83 Found: C 49.16, H, 5.92; N, 9.86. Example 103 IR (KBr): 3350, 2971, 2859, 1672, 1629, 1537, 1442, 1247, 1047 cm -1 NMR (DMSO-d 6, δ): δ, 96 (3H, d, J = 6.8Hz), 1.0-1.2 (6H, m), 1.2-1.6 "(12H, m), 1.7-2.5 (8H, m), 2.5-2.6 (1H, m), 3.2-3.6 (7H, m), 3.7-4.5 (16H, m), 4.76 (2H, d, J = 5.6Hz), 4.8-5.1 (5H, m), 5.09 (1H, d, J = 5.5Hz), 5.16 (1H, d, J = 3.1Hz), 5.23 (1H, d, J = 5.5Hz), 5.51 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (2H, m), 7.0-7.1 (3H, m), 7.3-7.5 (3H, m), 7.67 ( 2H, d, J = 6.9Hz), 7.71 (2H, d, J = 6.9Hz), 7.95 (2H, d, J = 8.4Hz), 8.05 (1H, d, J = 7.0Hz), 8.23 (1H, d, J = 7.7Hz), 8.70 (1H, d, J = 7.0Hz), 8.84 (1H, s) Vy FAB MASS : m / z = 1377, 1 (M + Na +)

Elemental Analysis calculated for <360Η83Ν8θ24Ν33 · 5Η2θ C 49.86, H 6.49, N 7.75

Example 104 172 Found: C 49.74, H 6.73, N 7.68 IR (KBr): 3349, 2937, 2858, 1672, 1629, 1537, 1444, 1249, 1047 cm -1 NMR (DMSO-d δ): 0.96 (3H, d, J = 6.7Hz), 1.08 (3H, d, J = 5.6Hz), 1.2-1.7 (14H, m), 1.7-. 2.1 (5H, m), 2.1-2.4 (5H, m), 2.5-2.6 (1H, m), 3.1-3.2 (1H, m), 3, 4-3.6 (4H, m), 3.7-4.5 (16H, m), 4.77 (2H, d, J = 5.7Hz), 4.8-5.2 (5H, m) ), 5.09 (1H, d, J = 5.6Hz), 5.16 (1H, d, J = 3.1Hz), 5.24 (1H, d, J = 4.5Hz), 5.51 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (2H, m), 7.0-7.1 (3H, m), 7.3-7.5 (3H, m), 7.6-7.8 (4H, m), 7.96 (2H, d, J = 8.4Hz), 8.10 (1H, d, J = 8.4Hz), 8.24 (1H, d, J = 7.7Hz), 8.71 (1H, d, J = 7.0Hz), 8.89 (1H, s) FAB MASS m / z 1386.5 (M + Na +)

Elemental Analysis calculated for C 6 H 8 N 8 O 23 NaS-6H 2 O C 49.76, H 6.43, N 8.56 Found: C 49.99, H 6.39, N 8.52.

Example 105 IR (KBr): 3350, 2933, 2856, 1664, 1631, 1604, 1511, 1450, 1243, 1045 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H, t, J = 6, 7Hz), 0.96 (3H, d, J = 6.5Hz), 1.05 (3H, d, J = 5.7Hz), 1.2-1.5 (8H, m), 1.6- 2.0 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.0-3.3 (5H, m), 3.6-4.4 (20H, m), 4.7-5.1 (7H-, m), "5.10 (1H, d, J = 5.5Hz), 5.16 (1H, d, J = 3.1Hz, 5.27 (1H, d, J = 4.5Hz), V 5.51 (1H, d, J = 6.0Hz), 6.7-7.1 (9H, m), 7.2-7.5 (3H, m), 8.0-8.2 (2H, m), 8.2-8.4 (1H, m), 8.4-8.6 ( 1H, m), 8.66 (1H, d, J = 2.2Hz), 8.85 (1H, s) FAB MASS: m / z = 1360 (M + NaH): Elemental analysis calculated for C58H80NiO22SNa-6H2O: Found: C, 48.16; H, 6.41; N, 10.65 Found: C, 47.91; H, 6.31; N, 10.56. Example 106 IR (KBr): 3369, 3345, 2935, 1672, 1629. , 1511, 1245, 1047 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), 1.06 (3H, d, J = 5.8Hz), 1.3- / 1.6 (10H, m), 1.6-2.0 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.20 (3H, s), 3.28 (2H, t, J = 6.4Hz), 3.1-3.4 (5H, m), 3.7-4.5 (20H) ,; m), 4.7-5.1 (7H, m), 5.08 (1H, d, J = 5.5Hz), 5.15 (1H, d, J = 3.1Hz), 5.23 (1H, d, J = 4.5Hz), 5.48 (1H, d, J = 5.8Hz), 6.73 (1H, d, J = 8.2Hz), 6.82 (2H, d, J = 9.1Hz), 6.94 (2H, d, J = 9.1Hz), 6.9-7 , 0 (1H, m), 7.04 (1H, s), 7.3-7.5 (3H, m), 8.0-8.1 (2H, m), 8.27 (1H, d) , J = 7.7Hz), 8.49 (1H, d, J = 7.0Hz), 8.66 (1H, d, J = 2.2Hz), 8.84 (1H, s) FAB MASS: m / z = 1404 (M + Na +) 173

Example 107 IR (KBr): 3357, 1647, 1631, 1537, 1444, 1249, 1049 cm -1 NMR (DMSO-d 6, δ): 0.9-1.1 (6H, m), 1.09 (3H) , d, J = 5.9Hz), 1.6-2.4 (8H, m), 2.4-2.5 (1H, m), 3.1-3.3 (1H, m), 3 , 6-4.5 (16H, m), 4.8-5.2 (7H, m), 5.10 (1H, d, J = 5.6Hz), 5.17 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 5.9Hz), 5.55 (1H, d, J = 5.9Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H, m), 7.0-7.6 (6H, m), 7.73 (2H, d, J = 8.7Hz), 7.86 (2H, d, J) 8.5Hz), 8.0-8.3 (8H, m), 8.84 (1H, s), 8.9-9.0 (1H, m) FAB MASS: m / z = 1379, 4 (M + Na) +

Elemental Analysis calcd for C8H12N4O2O4SaNa2O3O2 C 48.36, H 5.57, N 9, 56 Found: C 48.18, H 5.60, N 9.36.

The target compounds (108) to (117) were obtained according to Example 27.

Example 108 IR (KBr): 3350, 2933, 1670, 1627, 1521, 1436, 1272, 1047 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 6.7Hz), δ , 92 (3H, d, J = 6.7Hz), 1.1-: "1.4 (11H, m), 1.7-2.4 (9H, m), 3.1-3.2 ( 1H, m), 3.5-5.4 (27H, m), V1.6-6.6-7.2 (8H, m), 7.5-7.8 (3H, m), 7.8 -8.0 (3H, m), 8.1-8.8 (3H, m) FAB MASS: m / z = 1249.4 (M + Na +)

Elemental Analysis calculated for C52H71N10O2iNaS -7H2O C 46.15, H 6.33, N 10.35! Found: C, 46.12; H, 6.35; N, 10.24

Example 109: "IR (KBr pellet): 3361, 2933, 2856, 1670, 1652, 1616, 1540, 1508, 1448, 1261, 1047 cm -1 NMR (DMSO-d 6, δ): 0.86 (3H) , t, J = 6.6Hz, 0.97 (3H, d, J = 6.8Hz), 1.12 (3H, d, J = 6.8Hz), 1.2-1.5 (10H, m), 1.7-2.0 (5H, m), 2.2-2.6 (4H, 7µm), 3.1-3.2 (1H, m), 3.7-4, 4 (16H, m), 4.8-5.3 (10H, m), 5.59 (1H, d, J = 6.0Hz), 6.7-6.9 (3H, m), 7 , 0-7.4 (7H, m), 7.8-8.2 (4H, m), 8.8-1.9 9.0 (2H, m) FAB MASS: m / z = 1280 , 3 (M + Na +)

Elemental Analysis calculated for C54H72N9023NaS-7H2O C 46, 45, H 6.21, N 9.03

Example 110 174 Found: C 46.68, H 6.44, N 9.03 IR (KBr): 3350, 2931, 1670, 1627, 1540, 1436, 1276, 1047 cm -1 NMR (DMSO-d 6, δ) 0.87 (3H, t, J = 6.8Hz), 0.93 (2H, d, J = 8.8Hz), 1.08 (2H, d, J = 5.9Hz), 1.2- 1.4 (4H, m), 1.5-1.7 (2H, m), 1.7-2.1 (3H, m), 2.1-2.4 (3H, m), 2, 6-2.7 (3H, m), 3.1-3.3 (1H, m), 3.6-4.5 (17H, m), 4.7- 5.4 (8H, m), 6, 73 (1H, d, J = 8.2Hz), 6.83 (2H, d, J = 8.2Hz), 7.0-7.1 (1H, m), 7.2-7.5 (5H) , m), 7.65 (2H, d, J = 8.2Hz), 7.74 (2H, d, J = 8.4Hz), 7.98 (2H, d, J = 8.4Hz) , 8.08 (1H, d, J = 8.5Hz), 8.25 (1H, d, J = 8.5Hz), 8.74 (1H, d, J = 7.6Hz), 8.7- 9.0 (1H, lev) FABM: m / z = 1231.2 (M + Na1)

Elemental Analysis calculated for C53H69NaO2iNaS-3H2O C 50.39, H 5.98, N 8.87 Found: C 50.34, H 6.25, N 8.90

Example 111 IR (KBr): 3353.6, 1670.1, 1652.7, 1623.8 cm -1 NMR (DMSO-d 6, δ): 0.96 (3H, d, J = 6.7Hz), , 07 (3H, d, J = 5.6Hz), 1.20-1.62 (8H, m), 1.62-2.00 (5H, m), 2.10-2.65 (4H, m), 3.20 (3H, s), 3.08-3.40 (1H, m), 3.30 (2H, t, J = 6.5Hz), 3.53-4.50 (15H, m) , 4.68-5.13 (9H, m), 5.16 (1H, d, J = 2.9Hz), 5.26 (1H, d, J = 4.5Hz), 5.53: "( 1H, d, J = 5.9Hz), 6.68-6.95 (4H, m), 6.95-7.11 (3H, m), 7.20-7.52 V: (3H, m) ), 7.55-7.95 (7H, m), 8.13 (1H, d, J = 8.4Hz), 8.31 (1H, d, I'd; J = 7.7Hz), δ , 53 (1H, d, J = 7.0Hz), 8.85 (1H, s). FAB MASS: m / z = 1331.5 (M + Na-1).

Elemental Analysis calculated for C58H77N8NaO23S-6H2O: C 49.15, H 6.33, N 7.91: Found: C 49.07, H 6.53, N 7.84, Example 112 IR (KBr): 3350, 2937, 1673, 1646, 1631, 1538, 1519, 1456, 1247, 1049,) cm -1 NMR (DMSO-d6, δ): 0.97 (3H, d, J = 6.6Hz), 1 , 07 (3H, d, J = 5.7Hz), 1.3-4.0 (2.5H, m), 2.5-2.6 (1H, m), 3.2-3, 4 (1H, m), 3.5-4.6 (2OH, m), 4.8-5.7 (1H, m), 6.73 (1H, d, J = 8.0Hz), 6.9-. 7.0 (2H, m), 7.0-7.2, ι '(3H, m), 7.3-7.6 (3H, m), 7.74 (2H, d, J = 8, 5Hz), 7.77 (2H, d, ', J = 8.3Hz), 8.02 (2H, d, J = 8.3Hz), 8.13 (1H, d, J = 8, 4Hz), 8.30 (1H, d, J = 7.7Hz), 8.77 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1389 (M + Na +) 175

Elemental Analysis calculated for C61H83N8024NaS-7H2O C 49.06, H 6.55, N 7.50 Found: C 49.03, H 6.54, N 7.56

Example 113 NMR (DMSO-d6, δ): 0.84 (3H, t, J = 6.7Hz), 0.96 (3H, d, J = 6.7Hz), 1.07 (3H, d, J = 5.9Hz), 1.1-1.3 (14H, m), 1.7-2.1 (5H, m), 2.2-2.5 (3H, m), 2.6-2 , 7 (1H, m), 3.1-3.3 (1H, m), 3.7-4.5 (16H, m), 4.7-5.1 (7H, m), 5.10 (1H, d, J = 5.5Hz), 5.16 (1H, d, J = 3.1Hz), 5.25 (1H, d, J = 4.5Hz), 5.49 (1H, d, J = 5.7Hz), 6.53 (1H, d, J = 3.1Hz), 6.73 (1H, d, J = 8.2Hz), 6.8-6.9 (2H, m), 7.05 (1H, m), 7.31 (1H, d, J = 8.1Hz), 7.4-7.6 (4H, m), 7.70 (1H, d, J = 6.7Hz), 8.08 (1H, d, J = 8.4Hz), 8.18 (1H, s), 8.31 (1H, d, J = 7.7Hz), 8.57 (1H, d, J = 7 , 0Hz), 8.85 (1H, s) FAB MASS: m / z = 1264 (M + Na +)

Elemental Analysis calculated for C Cs ^HNNNNNgC iNNaS-eE ^O requires C 48.03, H 6.57, N 9.34 Found: C 48.02, H 6.61, N 9.28.

Example 114 IR (KBr): 3350, 2937, 1668, 1631, 1537, 1247, 1047 cm -1 NMR (DMSO-d 6, δ): 0.85 (3H, t, J = 7.4Hz), 0.96 (3H, d, J = 6.5Hz), 1.07 (3H, d, J = 5.7Hz), 1.3-1.7 (7H, m), 1.7-2.1 (5H, m), 2.2-2.4 (3H, m), 2.6-2.7 (1H, m), 3.0-3.8 (16H, m), 3.8-4.6 ( 11H, m), 4.7-5.3 (6H, i "m), 6.73 (1H, d, J = 8.2Hz), 6.8-7.0 (2H, m), 7, 0-7.2 (3H, m), 7.3-7.5 V: (3H, m), 7.6-7.8 (4H, m), 7.96 (2H, d, J = 8 , 3Hz), 8.11 (1H, d, J = 8.2Hz), 8.26 (1H, d, J = 7.6Hz), 8.6-9.0 (2H, m), FAB MASS : m / z = 1319.4 (M + Na +)

Elemental Analysis calculated for C57H77N8023NaS-8H2O: C 47.50, H 6.50, N 7.77 · Found: C 47.72, H 6.85, N 7.85 (Example 115 V, IR KBr): 3350, 1666, 1631, 1546, 1276, 1247 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 7.5Hz), 1.08 (3H, d, J = 5.7Hz), 1.4-1.6 (4H, m), 1.6-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.23 (3H, s), 3.3-3.5 (2H, m), 3.7-4.5 (16H) , m), 4.79 1: 1 (2H, d, J = 6.2Hz), 4.8-5.1 (5H, m), 5.11 (1H, d, J = 5.6Hz) , 5.18 (1H, 1H, J = 3.1Hz), 5.26 (1H, d, J = 4.4Hz), 5.54 (1H, d, J = 5.7Hz), 6, 73 (1H, d, J = 8.1Hz), 6.8-7.0 (2H, m), 7.0-7.1 (3H, m), 7.3-7.5 (3H, m) ), 7.6-7.9 (8H, m), 8.01 (2H, d, J = 8.4Hz), 8.08 (1H, d, J = 8.4Hz), 8.32 (1H , 176 d, J = 7.7Hz), 8.80 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1353.9 (M + Na +).

Elemental Analysis calculated for CΗΗΗ75Ν8023Ν33 · 9.5H2O C 47.96, H 6.31, N 7.46 Found: C 47.97, H 6.25, N 7.41.

Example 116 IR (KBr): 3450, 2935, 1675, 1650, 1540, 1513, 1454, 1047 cm -1 NMR (DMSO-d 6, δ): 0.97 (3H, d, J = 6.7Hz), 1.09 ( 3H, d, J = 5.9Hz), 1.60 (6H, s), 1.7-2.4 (6H, m), 2.5-2.6 (1H, m), 3.1- 3.6 (5H, m), 3.7-4.5 (14H, m), 4.7-5.0 (3H, m), 5.0-5.2 (4H, m), 5, 11 (1H, d, J = 5.5Hz), 5.18 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.56 (1H, d , J = 6.0Hz), 6.8-7.5 (9H, m), 7.84 (2H, d, J = 8.8Hz), 8.0-8.4 (6H, m), δ , 85 (1H, s), 8.91 (1H, d, J = 7.0Hz) FAB MASS: m / z = 1328 (M + Na) +

Elemental Analysis calculated for C55H68N11O2iS2Na-8H2O C 45.55, H 5.84, N 10.62 Found: C 45.62, H 5.70, N 10.54

Example 117 IR (KBr): 3350, 2939, 1664, 1627, 1531, 1446, 1249, 1049 cm -1 NMR (DMSO-d 6, δ): 0.8-1.0 (6H, m), 1.4 -1.9 (9H, m), 2.0-2.5 (4H, m), 3.1-3.2 (1H, m), 3.22 (3H, s), 3.3-3 , 4 (2H, m), 3.51 (2H, s), 3.6V. 4.4 (16H, m), 4.7-5.2 (7H, m), 5.07 (1H, d, J = 5.6Hz), 5.17 (1H, d, J = 3.1Hz) ), 5.23 (1H, d, J = 4.5Hz), 5.54 (1H, d, J = 5.9Hz), 6.7-6.8 (3H, m), 7.0-7 , 4 (8H, m), 7.5-7.7 (4H, m), 7.70 (4H, s), 8.1-8.2 (2H, m), 8.51 (1H, d) , J = 7.0Hz), 8.83 (1H, s) &lt; 1 &gt; FAB MASS: m / z = 1367.6 (M + Na &lt; + &gt;) V: Elemental analysis calculated for C61H77N8023SNa-6.5H2O C 50.01, H, 6.20; N, 7.66; Found: C, 50.30; H, 6.50; N, 7.75.

To a solution of the target compound (61) (0.25 g) in methanol (50 ml) was added dry 10% palladium on carbon (0.2 g) and stirred for 6 hours under a hydrogen atmosphere. The palladium / carbon was filtered off and the filtrate evaporated under reduced pressure to give the target compound: 118 (179 mg).

IR (KBr): 3400, 1668.1, 1627, 6 cm -1 NMR (DMSO-d 6, δ): 0.92 (3H, d, J = 6.7Hz), 1.1 - 2.45 (40H) , m), 3.20 (3H, 177 s), 3.28 (2H, t, J = 6.5Hz), 3.0-3.4 (1H, m), 3.5-4.7 ( 14H, m), 4.95-5.5 (12H, m), 6.55 (1H, d, J = 8.4Hz), 6.84 (1H, s), 6.86 (1H, d, J = 8.4Hz), 7.0-7.3 (4H, m), 7.9-8.3 (4H, m) FAB MASS: m / z = 1292 (M + Na)

Elemental Analysis calculated for C54H88Ng022SNa-5H20 C 47.67, H 7.26, N 9.26 Found: C 47.72, H 7.35, N 8.95.

The target compounds (119) to (121) were obtained according to Example 118. Example 119 NMR (DMSO-d6, δ): 0.87 (3H, t, J = 6.6Hz), 1.00 (3H, d, J = 7.3Hz), 1.03 (3H, d, J = 6.0Hz), 1.2-1.5 (4H, m), 1.5-2.0 (5H, m), 2.1-2.7 (8H, m), 3.17 (1H , m), 3.6-4.5 (14Ή, m), 4.65-5.7 (12H, m), 6.72 (1H, d, J = 8.1Hz), 6.75 (1H , s), 6.80 (1H, d, J = 8.1 Hz), 7.05 (1H, s), 7.1-7.7 (15H, m), 8.0-8.6 (4H) , m), 8.85 (1H, s) FAB MASS: m / z = 1274 (M + Na)

Elemental Analysis calculated for C Css + ^NCClCSNa ^H HO C 47.93, N 6.43, N 9, 15 Found: C 48.12, N 6.56, N 9.03

Example 120 IR (KBr): 3355.5, 1672.0 1629.6 cm -1 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6, 6Hz), 0.98 (3H) , d, J = 6.5Hz), 1.03: (3H, d, J = 6.0Hz), 1.2-2.6 (21H, m), 3.18 (1H, m), 3, 6-4.5 (16H, m), δ: 4.65-5.55 (12H, m), 6.6-7.5 (10H, m), 8.0-8.6 ( 4H, m), 8.89 (1H, s), FAB MASS: m / z = 1256 (M + Na)! Example 121 IR (KBr): 3357.5, 1660.4, 1629.6, 1249 , 6 cm -1 NMR (DMSO-d6, δ): 0.86 (3H, t, J = 6.6Hz), 0.96 (3H, d, J = 6.8Hz), 1.03 '' ( 3H, d, J = 6.0Hz), 1.1-1.5 (12H, m), 1.6-2.0 (5H, m), 2.0-2.5 (4H, m), 3.07 (1H, m), 3.5-4.5 (16H, m), 4.6-5.6 (12H, m), 6.72 (II-d, J = 8, 1Hz) ), 6.7-6.9 (4H, m), 7.04 (1H, s), 7.16 (1H, s), 7.1-7.5 (2H, m), 7.25 ( 2H, d, J = 8.6Hz), 8.0-8.2 (3H, m), 8.46 (1H, d, J = 7Hz), I'd 8.84 (1H, s) FAB- MASS: m / z = 1256 (M + Na) &lt; - &gt; / Elemental Analysis calculated for C18H19N3O3C3SNa-1H2O td C 45.91, H 6.67, N 9.27 Found: C 45.98, H 6.67. , N 9.10

Example 122 178

A solution of the target compound (11) (795 mg) in water (16 ml) was allowed to stand for 240 hours. The solution was column chromatographed with ODS (YMC gel ODS-AMS50) and eluted with 25% CH3CN / H2O. The fractions containing the target compound were combined and the acetonitrile removed under reduced pressure. The residue was lyophilized to give the target compound (123) (38 mg).

IR (KBr): 3361, 2956, 2875, 1668, 1627, 1521, 1249, 1047 cm -1 NMR (DMSO-d 6, δ): 0.8-1.5 (19H, m), 1.6-2 , 4 (13H, m), 3.1-3.2 (1H, m), 3.5-4.1 (12H, m), 4.1-4.7 (10H, m), 4.9 -5.6 (5H, m), 5.98 (1H, d, J = 10.6Hz), 6.36 (1H, d, J = 10.6Hz), 6.7-7.3 (12H, m), 7.4-8.0 (7H, m) FAB MASS: m / z = 1273.1 (M + Na +)

Elemental Analysis calculated for C55H71N8022NaS-11H2O C 45.58, H 6.47, N 7.73 Found: C 45.83, H 6.26, N 7.75.

The target compound (123) was obtained according to Example 118.

Example 123 IR (KBr): 3349.7, 1670.1, 1627, 6 cm -1 NMR (DMSO-d 6, δ): 0.87 (3H, t, J = 7.2Hz), 0.96 (3H) , d, J = 6.7Hz, 1.13: (3H, d, J = 5.7Hz), 1.18-1.55 (10H, m), 1.58-2.08 (5H, m) ), 2.08-2.90: (4H, m), 2.90-3.30 (2H, m), 3.60-4.50 (17H, m), 4.70-5.70 ( 12H, m):: v; 6.65-7.60 (11H, m), 7.80 (2H, levs), 7.95-8.23 (2H, m), 8.75 (1H, d, J = 7.0Hz), 8.85 (1H, s) FAB MASS: m / z = 1114.4 (M-SO4-2) 1 Elemental analysis calcd for 052-77-902-3.3-620: C, 47.88; H, 6.88; N, 9.66. : C 47.60, H 6.74, N 9.53: 11 The following compound (124) was obtained according to example 1.

"Example 124 h": IR (KBr): 3324, 2937, 2873, 1664, 1629, 1442, 1257 cm -1 NMR (DMSO-d 6, δ): 0.91 (3H, t, J = 7.1 Hz) ), 0.96 (3H, d, J = 6.7Hz), 1.09 (3H, d, J = 5.7Hz), 1.3-1.5 (4H, m), 1.7-2 , 6 (9H, m), 3.1-3.3 (1H, m), Λ; 3.7-4.6 (16H, m), 4.7-5.1 (7H, m), 5.11 (1H, d, J = 5.6Hz), 5.17 (1H, d, J = 3.1Hz), 5.26 (1H, d, J = 4.5Hz), 5.55 (1H, d, J = 5.8Hz), 6.7-6.9 (3H, m), 7 , 0-7.6 (6H, m), 7.97 (2H, d, J = 8.8Hz), 8.0-8.4 (6H, m), 179 8.85 (1H, s), 8.92 (1H, d, J = 7.0Hz) APCI MASS: m / z = 1331 (M + Na +)

Elemental Analysis calculated for C55H69N10O22NaS2: C 45.45, H 5.89, N 9.64 Found: C 45.71, H 5.68, N 9.60

Claims (12)

1. Polypeptide Compound of the Following General Formula (I): HO OH HO O \ / I V-NH) H3 C2 \ X / ^ Hh-r1 '- ^ y = o HO \ = 0 HN OH VO = / Wherein R 1 is (C 1 -C 6) alkanoyl, which is substituted with pyrazolyl, which contains (C 1 -C 6) alkyl and phenyl, which contains (C 7 -C 20) alkoxy; (C1-C6) alkoxy (C7-C20) alkanoyl, which (C7-C20) alkanoyl may contain amino or protected amino; ,; , benzoyl which is substituted by cyclo (C4-C6) alkyl containing (C1-C6) alkyl; indolylcarbonyl containing (C7-C20) alkyl; naphthoyl containing (C 1 -C 6) alkyl; naphthoyl containing (C 7 -C 20) alkyl; Benzoyl substituted with phenyl containing (C 1 -C 6) alkoxy (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; benzoyl substituted with phenyl containing (C 1 -C 6) alkoxy (C 1 -C 6) alkoxy; 'benzoyl substituted with phenyl containing phenyl containing (Qr: "; C6) alkoxy- (C1-C6) alkoxy; 1;": benzoyl substituted with phenyl containing tetrahydropyranyloxy (C7) Benzoyl substituted with phenyl containing phenoxy (C 1 -C 6) alkoxy; (C 1 -C 6) alkanoyl substituted with oxazolyl containing phenyl containing (C 7) -C20) alkoxy; 188 (C7-C20) alkanoyl with hydroxy; (C7-C20) alkanoyl with benzyl and hydroxy; 3-methyltridekenoyl; (C1-C6) alkanoyl substituted with pyridyl or pyridazinyl where both Containing 1-3 substituents selected from the group consisting of (C7-C20) alkoxy, (C7-C20) alkoxy (C1-C6) alkyl, phenyl with (C7-C20) alkoxy, phenyl substituted by phenyl containing (C 1 -C 6) alkoxy, piperazinyl substituted by phenyl, containing (C 7 -C 20) alkoxy, piperazinyl substituted by phenyl containing (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, and piperazinyl, which are substituted d with phenyl containing (C 1 -C 6) -10 alkoxy; (C 1 -C 6) alkanoyl, which is substituted with benzothiophenyl, which may contain 1-3 (C 7 -C 20) alkoxy; (C1-C6) alkanoyl, which is substituted with benzo [b] furanyl, which may contain 1-3 substituents selected from the group consisting of (C7-C20) alkoxy and (C1-C6) alkyl; (C1-C20) alkanoyl, which is substituted by benzo-oxazolyl, which may contain 1-3 substituents selected from the group consisting of (C7-C20) alkyl, phenyl containing (C1-C6) alkoxy, phenyl, which is substituted by phenyl containing (C 1 -C 6) alkyl and pyridyl containing (C 7 -C 20) alkoxy; (C 1 -C 6) alkanoyl substituted with piperidyl or piperazinyl, both of which may contain 1-3 substituents selected from the group consisting of phenyl containing (C 7 -; C 20) alkoxy, and naphthoyl containing (C 20) alkoxy; ; phenyl (C3-C6) alkenoyl, which is substituted by phenyl, which may contain 1-3 substituents: 1,1, tuents selected from the group consisting of (C1-C5) alkoxy, (C1-C6) alkyl, (C7 -C 20) alkyl, (C 1-4, C 6) alkoxy (C 1 -C 6) alkyl, halogen (C 1 -C 6) alkoxy, (C 2 -C 6) alkenyloxy, halogen (C 7 -C 20) alkoxy; , And (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; naphthyl (C3-C6) alkenoyl, which may contain 1-3 (C7-C20) alkoxy; 2-propynoyl (2- or 3-) butynoyl, (2- or 3- or 4-) pentynoyl, (2- or 3- or 4-or 5-) hexynoyl, each of which may contain 1-3 substituents selected from the group consisting of naphthyl containing (C 7 -C 20) alkoxy and phenyl substituted phenyl containing (C 1 -C 6) alkyl; . <-1 phenyl (C2-C6) alkanoyl substituted with phenyl containing 1-3 substituents selected from the group consisting of (C1-C6) alkoxy, (C7-C20) alkoxy, (C1-C6) ) alkyl, (C7-> C20) alkyl and phenyl containing (C1-C6) alkoxy (C1-C6) alkyl, where phenyl (C2-C6) -alkyl: in noyl may contain hydroxy, oxo, protected amino or amino; (C2-C6) alkanoyl substituted with naphthyl containing (C7-C20) alkoxy; 189 benzoyl substituted with pyrrolidinyl, imidazolidinyl, piperidyl or piperazinyl, each of which may contain 1-3 substituents selected from the group consisting of phenyl containing (C 1 -C 6) alkoxy, phenyl containing (C 7 C20 alkoxy, phenyl containing (C1-C6) alkyl, phenyl containing (C1-C6) alkoxy (C7-C20) alkoxy, phenyl containing (C7-C20) alkenyloxy, piperidyl substituted with phenyl, containing (C1-C6) alkoxy, piperidyl, cyclo (C4-C6) alkyl containing phenyl, phenyl containing cyclo- (C4-C6) alkyl and phenyl substituted with triazolyl containing oxo and (C 1 -C 6) alkyl, wherein benzoyl may contain halogen; benzoyl substituted with oxazolyl, iso-oxazolyl or oxadiazolyl, each of which may contain 1-3 substituents selected from the group consisting of (C 7 -C 20) alkyl, phenyl containing (C 1 -C 6) alkoxy, phenyl, containing (C7-C20) alkoxy, phenyl containing (C1-C6) alkoxy (C7-C20) alkoxy, phenyl substituted with phenyl containing (C1-C6) alkoxy; benzoyl substituted with pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl or tetrazolyl, each of which may contain 1-3 substituents selected from the group consisting of (C 7 -C 20) and phenyl containing (C 1 -C 6) alkoxy; benzoyl substituted with thiazolyl, isothiazolyl, thiadiazolyl or dihydrotiazinyl, each of which may contain 1-3 substituents selected from the group consisting of phenyl, containing (C1-C5) alkoxy, phenyl containing (C7-C20) alkoxy, cyclo- (C4-C6) alkyl, containing (C1-C6) alkyl, phenyl substituted with phenyl containing (C1-C6) alk-: oxy, phenyl containing cyclo (C4-C6) alkyl phenyl containing piperidine and phenyl: v containing (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; benzoyl substituted with phenyl containing (C1-C6) alkoxy (C7-C20) alkoxy; Benzoyl substituted with phenyl containing (C 1 -C 6) alkyl; benzoyl substituted with phenyl containing (C 7 -C 20) alkyl; and its pharmaceutically acceptable salt. A compound according to claim 1, wherein R 1 is benzoyl which is substituted by pipe 1-razinyl, which may contain 1-3 substituents selected from the group consisting of phenyl, 2, with (C 1 -C 6 ) alkoxy, phenyl containing (C7-C20) alkoxy, phenyl containing (C1-C6) - alkyl, phenyl containing (C1-C6) alkoxy (C7-C20) alkoxy, phenyl containing (C7- C20) alkenyloxy, piperidyl substituted with phenyl containing (C1-C6) alkoxy, cyclo-; > · ,; (C4-C6) alkyl containing phenyl, phenyl containing cyclo (C4-C6) alkyl, and phenyl substituted with triazolyl, containing oxo and (C1-C6) alkyl, 190 wherein benzoyl may contain halogen; benzoyl substituted with iso-oxazolyl which may contain 1-3 substituents selected from the group consisting of (C 7 -C 20) alkyl, phenyl containing (C 1 -C 6) alkoxy, phenyl containing (C 7 -C 20) alkoxy phenyl containing (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy, phenyl substituted by phenyl containing (C 1 -C 6) alkoxy; benzoyl substituted with phenyl containing (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; benzoyl substituted with phenyl containing (C 1 -C 6) alkyl; benzoyl substituted with phenyl containing (C 7 -C 20) alkyl; phenyl (C3-C6) alkenoyl, which is substituted with phenyl, which may contain 1-3 substituents selected from the group consisting of (C1-C6) alkoxy, (C1-C6) alkyl, (C7-C20) alkyl , (C1-C6) alkoxy (C1-C6) alkyl, halogen (C1-C6) alkoxy, (C2-C6) alkenyloxy, halogen (C7-C20) alkoxy and (C1-C6) alkoxy (C7-C20) alkoxy; benzoyl substituted with thiadiazolyl, which may contain 1-3 substituents selected from the group consisting of phenyl containing (C1-C6) alkoxy, phenyl containing (C7-C20) alkoxy, cyclo (C4-C6) alkyl , which contains (C1-C6) alkyl, phenyl substituted by phenyl, which contains (C1-C6) alkoxy, phenyl which contains cyclo (C4-C6) alkyl, phenyl containing piperidyl, and phenyl containing (C1-6) 6) alkoxy (C 7 -C 20) alkoxy; or benzoyl substituted with oxadiazolyl, which may contain 1-3 substituents selected from the group consisting of phenyl containing (C 1 -C 6) alkoxy, phenyl, containing; pours (C7-C20) alkoxy, phenyl containing (C1-C6) alkoxy (C7-C20) alkoxy, (C7-C20) alkyl,; and phenyl which is substituted phenyl containing (C 1 -C 6) alkoxy. The compound of claim 2, wherein R 1 is benzoyl substituted with phenyl containing (C 1 -C 6) alkoxy (C 7 -C 20) alkoxy; or, 1; ·, Benzoyl, which is substituted with phenyl containing (C 1 -C 6) alkyl. The compound of claim 2, wherein R 1 is' ... benzoyl, which is substituted with piperazinyl, which may contain phenyl, which contains (C 1 -C 6) alkoxy; 1 -. ' benzoyl substituted with isoxazolyl, which may contain phenyl, which contains (C1-C6) alkoxy; ; benzoyl, which is substituted with thiadiazolyl, which may contain phenyl, which contains: 1 µl (CrC6) alkoxy (C7-C20) alkoxy; or 191 benzoyl substituted with oxadiazolyl which may contain phenyl containing (C 1 -C 6) alkoxy. The compound of claim 2, wherein R 1 is phenyl (C 3 -C 6) alkenoyl, which is substituted phenyl, which may contain (C 1 -C 6) alkoxy. The compound of claim 4, wherein R 1 is benzoyl, which is substituted with isoxazolyl, which may contain phenyl, which contains (CrC 6) alkoxy. 10 A compound according to claim 1, wherein R 1 is -CO-C 2 HVVCVO- (CH 2:> 4 CH 3 N 0) and its pharmaceutically acceptable salt. A process for the preparation of a polypeptide compound of formula [I]: I-10 OH no 0 - /) NH_R1 '- N \ = O H0. V = ° H N OH: ''; y - / n 0 = / ^ fI] H ° / - (';, / = / OH 0 Il \ _ / O / - HO 15': 'where R1 is defined in claim 1; of, that a compound of the formula: 192 HO OH HO O \ -is X / · -NH) J \ / f-NH2 H0> ^ = ° HN OH M> O = Mc '3 H2N O = / HO \ -NH / V \ _ / ΧΧχ / ΌΗ il / = \ X ° H 0 HO-SOJ> O / - 'HO or its reactive derivatives in the amino group or its site, is reacted with a compound of the formula: R1 - OH [III] where R1 represents the same as in claim 1, or its reactive derivative in the carboxy group or its site, wherein a compound [I] of the formula:; ''; HO OH HO O \ - (»3c ^ AX“ Xr1: 1, '—n "\ = o', ('' H0, HN OH 0 = (^ CH3 [x],, H2N 0 = / '" HO \ Wherein NH represents the same as in claim 1, or its site is obtained. A pharmaceutical composition which contains as an active component a compound of claim 1 or its pharmaceutically acceptable carrier in admixture with a pharmaceutically acceptable carrier or additive. The use of a compound according to claim 1 or its pharmaceutically acceptable site for the manufacture of medicaments. The compound of claim 1, or its pharmaceutically acceptable site for use as a medicament. 10 The use of a compound according to claim 1 or its pharmaceutically acceptable site for the manufacture of a medicament for the host and prophylaxis of infectious diseases. 'I